Announcement • Jul 17
Kalaris Therapeutics Reports Positive Additional Data From Phase 1a Single Ascending Dose Trial Of TH103 In Neovascular Age-Related Macular Degeneration Kalaris Therapeutics announced positive additional data from its Phase 1a single ascending dose (SAD) trial of TH103 in neovascular age-related macular degeneration (AMD). Data from the expanded cohorts build on previously reported positive findings from the trial, with additional patients showing improvements in vision and retinal anatomy and further supporting the potential for extended treatment durability after a standard four-dose loading regimen. The updated SAD results will be presented at the American Society of Retina Specialists (ASRS) Annual Meeting. The expanded Phase 1a SAD dataset now includes a total of 17 treatment-naive patients, as well as an additional 3 treatment-experienced patients which were included in the safety cohort. All 20 patients completed six months of follow-up. Consistent with Kalaris’ previously reported findings, the expanded efficacy analysis, which includes the 17 treatment-naïve patients, continued to demonstrate robust structural and functional improvements. TH103 plasma pharmacokinetic findings continued to suggest greater intraocular retention, with 27- to 53-fold lower Cmax compared to current leading anti-VEGF agents on a molar equivalence basis. Additionally, the time to retreatment results further supported the hypothesis that increased intraocular retention may contribute to prolonged biological activity: following only a single TH103 injection, 41% of treatment-naïve patients (N=17) received a first retreatment at 4 months or later, 35% at 5 months or later, and 29% received no additional anti-VEGF treatment during the entire six-month follow-up period. Separately, after a single TH103 injection, time to retreatment in treatment-experienced patients (N=3) was extended by an average of 2 months compared with prior anti-VEGF treatment intervals. No cases of intraocular inflammation (IOI) were observed among the six patients treated at the 2.5 mg dose using product manufactured following process adjustments to reduce impurities. As previously reported, one patient treated at the 5 mg dose experienced transient IOI that resolved without sequelae. Enrollment in the Phase 1b/2 multiple-ascending dose trial of TH103 continues, with preliminary data on track for the first half of 2027. Building on these findings, Kalaris is actively enrolling and dosing patients in its ongoing Phase 1b/2 study aimed at evaluating a standard four-dose loading regimen of TH103 in treatment-naïve patients using an ascending-dose design. The study is designed to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of repeated TH103 intravitreal injections as well as time to retreatment following a complete loading course. Study results will inform dose selection for potential future Phase 3 trials of TH103, and Kalaris remains on track to share initial data from the Phase 1b/2 study in the first half of 2027. TH103 is a potential best-in-class, investigational dual-targeting biologic engineered by VEGF scientific discoverer Dr. Napoleone Ferrara to achieve extended intraocular retention with enhanced VEGF inhibition through optimized binding to VEGF receptor 1 ligands and concurrent heparan sulfate proteoglycan (HSPG) anchoring. It is a fully humanized, recombinant fusion protein designed for intravitreal delivery, with potential applications as a treatment for exudative and/or neovascular retinal diseases, such as neovascular AMD, diabetic eye disease and retinal vein occlusion. TH103 is currently being investigated in a Phase 1b/2 clinical trial in patients with neovascular Age-related Macular Degeneration (nAMD). 
