Oculis completes randomization in PREDICT-1, the first genotype-guided registrational trial in dry eye disease

Oculis Holding AG has completed randomization in PREDICT-1 (Personalized dRy Eye Disease Investigational Clinical Trial), the registrational study evaluating licaminlimab, a topical anti-TNFα eye drop, in patients with dry eye disease (DED) who carry a specific TNFR1 genotype.¹ The Zug, Switzerland–based company said it expects to report topline results around year-end 2026.

The milestone moves what Oculis describes as the first genotype-guided registrational trial in DED a step closer to a readout that will test whether a genetic biomarker can reliably identify the patients most likely to respond to an anti-inflammatory therapy.

Enrollment closes ahead of plan

PREDICT-1 randomized its first patient in June 2026.² At the time, Oculis said it planned to enroll approximately 160 patients, roughly two-thirds of whom would carry the target TNFR1 variant.² By early August, all planned sites had been activated and more than 45% of patients had been randomized, according to the company's second-quarter update.³ The final tally of 176 patients, two-thirds of them genotype-positive, exceeds that original target.¹ Optometry Times, a sister publication of Ophthalmology Times, covered the trial's launch in June.⁴

"Completing randomization in such a timeframe with a new modality demonstrates that genotype-driven development is crucial and precision medicine is urgently needed in DED," said Riad Sherif, MD, CEO of Oculis. "PREDICT-1 is an important operational milestone as we track toward topline results around year-end 2026."¹

Trial design

PREDICT-1 is a randomized, multicenter, double-masked, vehicle-controlled study. Its primary endpoint is the change from baseline at day 29 in the global ocular discomfort severity score among patients carrying the specified TNFR1 genotype. The same measure will be assessed across the overall study population as a key secondary endpoint, and the trial will also evaluate safety.¹ To improve efficiency, the study incorporated a genotype screening phase before enrollment.²

The design places symptom relief, rather than ocular surface signs, at the center of the registrational question. That choice is not without risk: Oculis has acknowledged that measurements of dry eye symptoms are inherently subjective, framing genotype enrichment as a way to select the patients most likely to show a measurable benefit.³

Building on phase 2 signals

The rationale for PREDICT-1 rests on earlier phase 2 work. In a prior phase 2 trial focused on DED symptoms, patients treated with licaminlimab experienced a statistically significant reduction in ocular discomfort compared with vehicle at Day 29, with onset of action observed as early as Day 14.^1,5

The phase 2b RELIEF trial, reported in 2024, evaluated licaminlimab on the signs of DED and included a prespecified subpopulation of 23 patients carrying the TNFR1-related genotype.⁶ As Ophthalmology Times reported at the time, the company observed a treatment effect favoring licaminlimab in that subgroup, positioning the genetic marker as a potential predictor of response.⁶ Across its phase 2 program, Oculis reports that the drug has been well tolerated.¹

Licaminlimab is a single-chain antibody fragment (scFv) developed specifically for ocular inflammatory disease. TNFR1 mediates TNFα-driven inflammation and apoptosis, and published research suggests that genetic variation in the TNF/TNFR1 pathway may help explain why inflammatory responses—including those on the ocular surface—differ between patients.^1,7 According to Oculis, a simple, noninvasive genetic test can identify carriers of the relevant variant.¹

The case for precision medicine in DED

The program arrives as thinking about DED continues to evolve. In an Ophthalmology Times Q&A published during Dry Eye Awareness Month, Esen K. Akpek, MD, of the Wilmer Eye Institute at Johns Hopkins, discussed how the TFOS DEWS III report has moved classification away from the aqueous-deficient vs evaporative dichotomy toward identifying root causes.⁸ Akpek pointed to reliable biomarkers and patient-centered outcome measures as the field's greatest unmet need on the path to true precision medicine, and the article highlighted anti-TNFα biologics among the emerging therapies pushing care toward mechanism-based treatment.⁸

Anat Galor, MD, MSPH, professor of ophthalmology at Bascom Palmer Eye Institute in Miami, Florida, made a similar case. "Dry eye disease is a highly heterogeneous condition, and treatment response can vary considerably between patients," she said. "As a result, selecting the right therapy often involves a lengthy trial-and-error process that can lead to patient dissatisfaction and early treatment discontinuation."¹

Galor added that the earlier licaminlimab findings provide a compelling rationale for PREDICT-1 and that she is looking forward to seeing whether the targeted approach can improve outcomes for patients.¹

The scale of that unmet need is considerable. Oculis estimates that approximately 40 million people in the US have DED, about half of whom are formally diagnosed, and roughly 10 million have moderate-to-severe disease requiring active treatment.¹ Citing published data, the company notes that only about 13% of patients achieve sustained relief and that 85% to 90% discontinue therapy within the first 6 months.¹ An estimated 13% to 19% of patients with moderate-to-severe DED—approximately 1.3 million to 1.9 million individuals—carry the relevant TNFR1 variant, according to the company.¹

What comes next

The year-end readout will be the first registrational test of whether genotype selection can turn a phase 2 subgroup signal into a confirmatory result. Key questions for clinicians will include the magnitude of benefit in genotype-positive patients, how licaminlimab performs in the broader population, and how genetic testing might fit into routine clinic workflow should the therapy reach the market.

Licaminlimab is an investigational drug and has not received regulatory approval for commercial use in any country.¹

References

1. Oculis Holding AG. Oculis completes randomization in PREDICT-1 registrational trial of licaminlimab for TNFR1-mediated dry eye disease. News release. October 19, 2026. Accessed October 19, 2026. https://investors.oculis.com/news-releases/news-release-details/oculis-completes-randomization-predict-1-registrational-trial

2. Oculis Holding AG. Oculis announces first patient randomized in PREDICT-1 registrational trial of licaminlimab, advancing precision medicine in dry eye disease. News release. June 9, 2026. Accessed October 19, 2026. https://investors.oculis.com/news-releases/news-release-details/oculis-announces-first-patient-randomized-predict-1

3. Oculis Holding AG. Oculis reports Q2 2026 financial results and provides company update. News release. August 6, 2026. Accessed October 19, 2026. https://mfn.se/one/a/oculis-holding/oculis-reports-q2-2026-financial-results-and-provides-company-update-b3f73c87

4. Oculis enrolls first patient in licaminlimab PREDICT-1 DED trial. Optometry Times. June 12, 2026. Accessed October 19, 2026. https://www.optometrytimes.com/view/licaminlimab-predict-1-trial-enrolls-first-patient-ded

5. Shettle L, et al. Topical anti-TNFα agent licaminlimab (OCS-02) relieves persistent ocular discomfort in severe dry eye disease: a randomized phase II study. Clin Ophthalmol. 2022.

6. Oculis announces positive topline results of phase 2b RELIEF trial. Ophthalmology Times. June 10, 2024. Accessed October 19, 2026. https://www.ophthalmologytimes.com/view/oculis-announces-positive-topline-results-of-phase-2b-relief-trial

7. Acuna K, et al. Impact of tumor necrosis factor receptor 1 (TNFR1) polymorphism on dry eye disease. Biomolecules. 2023.

8. Root cause–based dry eye classification and the shift toward precision medicine. Ophthalmology Times. July 15, 2026. Accessed October 19, 2026. https://www.ophthalmologytimes.com/view/root-cause-based-dry-eye-classification-precision-medicine