Kalaris has opened enrollment for a Phase 1b/2 multiple-ascending-dose study of TH103 in neovascular AMD, targeting up to 80 patients with four initial monthly intravitreal doses and a primary analysis one month after the last injection. Initial readout is guided for the second half of 2026. The program builds on an ongoing Phase 1a single-ascending-dose study with safety, preliminary efficacy, and PK data expected in the fourth quarter of 2025.
The core move is a redesign of Kalaris’ early clinical path: instead of a smaller Part 2 after the SAD, the company is jumping to a larger dose-finding study intended to set the Phase 3 dose and regimen. The MAD will evaluate safety and early vision/anatomic signals across multiple dose levels, followed by an extension phase to probe durability. It’s an operationally conventional design for retina centers—monthly loading followed by observation—meant to create a cleaner bridge to pivotal planning without committing too early to a fixed dosing interval.
Strategically, this looks like a bid to accumulate a more persuasive data package before negotiating a pivotal program in a crowded anti-VEGF market defined by durability claims. With faricimab cementing share on extended intervals and aflibercept 8 mg pushing to 12–16 weeks, any newcomer has to demonstrate either longer disease control or comparable outcomes with fewer injections. Kalaris’ messaging around “dual-action” inhibition and longer retinal residence positions TH103 squarely on the durability axis. The decision to front-load with four monthly doses suggests the company is aiming to emulate or exceed existing loading paradigms and then test interval extension in the extension phase. The redesign also spreads risk: if the SAD reveals dose-limiting inflammation or PK constraints, the Phase 1b/2 protocol can be tuned before broad activation.
For sites, the study aligns with current wet AMD workflows—intravitreal administration, OCT-centric outcomes, familiar safety monitoring—reducing training friction. The bigger challenge will be competing for eligible patients amid a steady flow of commercial options and trials chasing extended dosing. Inclusion criteria will drive feasibility: treatment-naïve enrollment is cleaner scientifically but harder operationally in regions where clinicians default to bevacizumab first-line; previously treated cohorts are easier to recruit but complicate signal detection. CROs and imaging core labs will recognize a standard playbook, but execution will hinge on tightly managed inflammation monitoring, adjudication of intraocular events, and consistent OCT acquisition to support dose-response modeling. Regulators will expect a pivot to active-controlled Phase 3 trials against contemporary standards with endpoints that test interval extension without sacrificing vision outcomes. Any hint of retinal vasculitis or occlusive events—issues that have derailed entrants before—will be determinative.
The near-term watch list is clear. The Q4 2025 SAD data will need to de-risk ocular inflammation and show an encouraging BCVA and central thickness signal after a single dose, alongside intraocular PK that supports extended retention. The Phase 1b/2 activation cadence, geographic footprint, and whether the extension phase adopts treat-and-extend rules will telegraph Kalaris’ pivotal intent. By late 2026, the company will need a coherent dose and interval hypothesis with enough durability evidence to justify an active-controlled Phase 3; otherwise, the timeline pushes into 2027 and beyond. Longer term, Kalaris must articulate how TH103 competes against entrenched brands and emerging sustained-delivery and gene therapy approaches, and whether it will partner for pivotal execution and commercialization. The bar is not a novelty; it is durable, inflammation-free control with fewer injections. That is the only thesis that will move sites, payers, and share in modern wet AMD.
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.
