Kalaris reports positive Phase 1a data for TH103 in neovascular AMD, showing improved vision, extended retreatment intervals, favorable safety, and Phase 1b/2 progress.
Written By: Shaik Yasmeen, PharmD
Reviewed By: Pharmacally Editorial Team
Kalaris Therapeutics has reported additional positive Phase 1a data for its investigational retinal therapy TH103, reinforcing earlier findings that suggest the candidate may provide durable vision benefits with extended treatment intervals in patients with neovascular age-related macular degeneration (nAMD). The expanded dataset also supports continued development of TH103, with initial results from the ongoing Phase 1b/2 multiple-ascending dose study expected in the first half of 2027.
Expanded Phase 1a Data Strengthen Early Clinical Evidence
The updated Phase 1a single ascending dose (SAD) study included 20 patients who completed six months of follow-up. The efficacy analysis comprised 17 treatment-naïve patients, while three treatment-experienced patients were enrolled in a separate safety cohort.
The expanded results were consistent with previously reported findings, showing sustained improvements in best-corrected visual acuity (BCVA) and retinal anatomy measured by optical coherence tomography (OCT). The additional patients reinforced the favorable structural and functional outcomes observed in the original cohorts.
The new pharmacokinetic data also continued to support prolonged intraocular drug retention. TH103 achieved plasma maximum concentrations (Cmax) that were 27- to 53-fold lower than leading anti-VEGF therapies on a molar equivalent basis, suggesting reduced systemic exposure while maintaining ocular activity.
Longer Treatment Durability Observed After a Single Injection
One of the most notable findings from the study was the extended interval before patients required additional anti-VEGF therapy.
Among the 17 treatment-naïve patients, 41% required their first retreatment at four months or later following a single TH103 injection. Thirty-five percent remained treatment-free for at least five months, while 29% completed the entire six-month follow-up period without requiring any additional anti-VEGF treatment.
The three treatment-experienced patients also demonstrated longer treatment intervals, with retreatment extended by an average of two months compared with their previous anti-VEGF regimens.
These findings further support the hypothesis that prolonged intraocular retention may translate into extended biological activity and reduced injection frequency, an important goal in managing neovascular AMD.
Favorable Safety Profile Supports Continued Development
Safety findings remained encouraging in the expanded analysis.
No cases of intraocular inflammation (IOI) occurred among six patients who received the 2.5 mg dose manufactured using an updated production process intended to reduce impurities. Investigators previously reported one case of transient IOI in a patient treated with the 5 mg dose. The event resolved without lasting complications.
The updated manufacturing process may help improve the therapy’s safety profile as clinical development advances.
TH103 Targets VEGF Through a Dual-Action Mechanism
TH103 is an investigational fully human recombinant fusion protein engineered by VEGF pioneer Dr. Napoleone Ferrara. Unlike conventional anti-VEGF therapies, the biologic combines optimized binding to VEGF receptor 1 ligands with anchoring to heparan sulfate proteoglycans (HSPGs), a strategy intended to increase intraocular retention and extend therapeutic activity after intravitreal administration.
If successful, the approach could reduce treatment burden for patients with retinal vascular diseases that require frequent anti-VEGF injections, including neovascular AMD, diabetic eye disease, and retinal vein occlusion.
Phase 1b/2 Trial Continues Enrollment
Commenting on the findings, Kalaris Chief Executive Officer Andrew Oxtoby said the expanded dataset strengthened confidence in TH103’s potential differentiation, citing the consistency of the visual, anatomical, and pharmacokinetic results across patients.
The company is continuing enrollment in its ongoing Phase 1b/2 multiple-ascending dose study, which evaluates a standard four-dose loading regimen in treatment-naïve patients with neovascular AMD. The trial is assessing safety, tolerability, pharmacokinetics, preliminary efficacy, and time to retreatment following repeated intravitreal injections.
The results will guide dose selection for future Phase 3 development, with preliminary Phase 1b/2 data expected during the first half of 2027.
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About the Writer
Shaik Yasmeen (LinkedIn) is a Pharm.D graduate with interests in clinical pharmacy, pharmacovigilance, and medical writing. She has gained experience through hospital clinical postings, patient case reviews, case presentations, and literature evaluation. Passionate about evidence-based healthcare, she is committed to creating accurate and engaging medical content while continuously expanding her professional knowledge.