No efficacy or safety data were released. Kalaris has begun enrolling a Phase 1b/2 multiple ascending dose study of TH103 in neovascular age-related macular degeneration, testing four initial monthly intravitreal injections across dose levels in up to 80 patients, with a primary analysis one month after the last injection and an extension phase to follow. The program builds on an ongoing Phase 1a single ascending dose study, with initial Phase 1a data targeted for Q4 2025 and preliminary readouts from the Phase 1b/2 in the second half of 2026. The new design replaces a smaller Part 2 that had been planned to follow Phase 1a.
The move signals an intent to compress the early-development arc and arrive at a Phase 3 dose-selection decision under a single, operationally consistent framework. Structurally, four monthly injections mirror standard loading regimens and position the primary analysis to capture durability signals in the immediate post-loading period. The extension phase suggests plans to study maintenance intervals and retreatment criteria before committing to pivotal comparators. TH103 is described as a dual-action construct intended to increase anti-VEGF inhibition and retinal retention, a profile that, if validated, would need to demonstrate either meaningfully longer dosing intervals or reduced visit burden versus today’s benchmarks.
The competitive bar in nAMD is high. Eylea HD and Vabysmo have set expectations around Q12–Q16 maintenance in a substantial share of patients, while biosimilars and alternative delivery approaches are reshaping cost and access dynamics. In that context, Kalaris’s dose-finding study will be judged on two fronts: a clean ocular safety profile—particularly intraocular inflammation and vasculitis, which remain class-sensitive issues—and early anatomic and functional signals that justify testing against active standards at extended intervals. The choice to replace a smaller Part 2 with a larger, multi-cohort Phase 1b/2 reads as a bid to generate a broader exposure-safety dataset and a more defensible dose-selection package for regulators and payers.
For research sites, the design is familiar and executable within retina clinic workflows: monthly visits for four injections, intensive OCT imaging, visual acuity assessments, and pressure monitoring, followed by protocol-driven extension follow-up. The lack of a comparator simplifies startup but places more weight on centralized imaging, masked grading, and adverse event adjudication to build confidence ahead of Phase 3. Enrollment feasibility should be favorable given nAMD prevalence, though competition from commercial care and parallel studies will require clear inclusion criteria, especially on prior anti-VEGF exposure and fluid tolerance. CROs and vendors should anticipate tight coordination across reading centers and safety oversight, with cohort escalation gating on ocular inflammation thresholds.
Looking ahead, the critical reveal comes in Q4 2025 when Phase 1a data will set expectations for inflammation rates, pharmacokinetics, and early anatomic effects. Those results will also clarify whether the Phase 1b/2 incorporates any randomized elements or retreatment algorithms that preview the pivotal strategy. If preliminary Phase 1b/2 data in 2H 2026 support dose selection, a Phase 3 start in 2027 is plausible, but the pivotal bar will require active comparators, extended dosing claims, and BCVA outcomes that at least match current leaders. Key risks remain differentiation in a crowded market, the need for unambiguous durability beyond loading, and the operational demands of scaling ophthalmic safety surveillance. Watch for updates on maintenance interval targets, comparator choice, and any expansion into DME and RVO that could diversify the value proposition—or stretch resources before a first proof point in nAMD.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
