Telios Pharmaceuticals, Inc. announced topline data from its phase 2 study examining TL-925 (ophthalmic emulsion 0.1%), an investigational candidate for the treatment of moderate to severe dry eye disease (DED).
Let’s start with Telios Pharma.
Founded in 2019 with headquarters in Redwood City, California and Bellevue, Washington, the privately-held, clinical stage biopharmaceutical company is developing novel targeted therapeutics to treat select blood cancers and ophthalmic diseases.
The key to its therapeutics: Bruton’s tyrosine kinase inhibitor (BTKi)
Explain this, please.
BTKi is a nonreceptor tyrosine kinase that holds a critical position in the signal transduction of the B-cell antigen receptor and other cell surface receptors.
Outside of the ophthalmic field, BTKis are increasingly replacing chemotherapy-based regimens for blood cancers such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL).
Previous research has also noted that current use of BTKi involves continuous, long-term administration.
Gotcha. Now this candidate.
Per Telios, TL-925 is a first-in-class topical (irreversible) BTKi formulated to:
- Prevent mast cell activation and degranulation
- Block the cytokine-driven inflammatory response
- Restore lacrimal unit homeostasis
The intent: the potential to modify and treat the underlying cause of specific diseases (ie: DED)
Gotcha. Now talk about this study.
Overseen by Ora Inc., the proof-of-concept, multicenter, randomized, double-masked phase 2 study (NCT05745064) examined the safety, tolerability, and efficacy of TL-925 vs a control.
A total of 107 patients with moderate to severe DED (diagnosed at least 6 months prior) were enrolled and dosed either TL-925 or the control, twice a day (BID), for 28 days total.
See here for the complete inclusion and exclusion participant criteria, per Clinical Trials.
And the outcome measures?
Measured to the end of day 29 (±2 days), they included:
- Primary
- Adverse events (AEs) during screening and treatment period
- Secondary
- Change from baseline in corneal and conjunctival staining
- Change from baseline in ocular discomfort (via the visual analog scale [VAS])
- Change from baseline best-corrected visual acuity (BCVA)
So what were the findings?
According to Telios, an intention-to-treat analysis demonstrated TL-925 to have a “clinically meaningful and statistically significant efficacy relative to vehicle control across multiple signs and symptoms.”
Go on …
A rapid onset of efficacy across “multiple ocular regions,” as well as a demonstration of favorable and consistent results in various environments support the candidate’s “differentiated” profile, the company reported.
Translation: TL-925 was found to be a safe, well-tolerated, and effective treatment for DED.
Expert input?
Ora’s Senior Vice President George Ousler, who served as lead investigator, noted TL-925’s potential to impact the underlying pathology of DED.I am highly encouraged by the breadth of positive results from this phase 2 study, “ he stated. “The results are among the most impressive that I have seen in my years working on dry eye clinical development programs.”
So what’s next?
Based on this positive data, a prospective, multicenter, randomized, double-masked, vehicle-controlled, parallel-arm phase 2b study (NCT06225973) has been initiated, according to Telios Pharma.
Per Clinical Trials, the study is expected to enroll an estimated 670 participants with moderate to severe DED, and will comprise two phases:
- Phase 1: 2-week screening phase/ run-in
- Phase 2: 6-week double-masked treatment phase
Additionally, a separate phase 2b study (NCT06153342) on TL-925—for allergic conjunctivitis (AC), this time—has “recently shown clinically meaningful and statistically significant improvements in both itching and redness,” the company reported.
And the significance?
Similarily, Gail Torkildsen, MD, a principal investigator of both the phase 2 DED and AC studies, indicated that the positive efficacy results for DED and AC “demonstrated that TL-925 can effectively and rapidly halt the cycle of inflammation.”“These data also validate TL-925’s potential to target the underlying inflammatory mechanisms driving these diseases,” Dr. Torkildsen stated. “It is increasingly apparent that TL-925 may represent a significant leap forward for the effective treatment of DED and AC.”