Kalaris Drug TH103 Shows Vision Gains, Hints at Longer AMD Dosing

By Brenda Thompson

BERKELEY HEIGHTS, N.J. – December 17, 2025 – Kalaris Therapeutics today announced encouraging initial data for its investigational drug TH103, signaling a potential breakthrough in the treatment of neovascular age-related macular degeneration (nAMD), a leading cause of vision loss in older adults. The results from a Phase 1a study showed that a single injection of the drug led to rapid and significant improvements in vision and retinal anatomy, with early evidence suggesting it could dramatically reduce the frequency of injections for patients.

For the millions living with nAMD, the current standard of care often involves frequent, burdensome injections directly into the eye to preserve sight. Kalaris's announcement offers a glimmer of hope for a less demanding treatment regimen, a key goal in a competitive therapeutic landscape. The positive data sent the company’s stock (NASDAQ: KLRS) surging in after-hours trading as investors and the medical community took note.

Potent Results from a Single Dose

The early-stage trial evaluated TH103 in 13 patients with nAMD who had not previously received treatment. The results at the one-month mark were striking. On average, patients experienced a 10-letter gain in best corrected visual acuity (BCVA) - a standard measure of vision on an eye chart. This level of improvement is highly competitive, stacking up well against the initial responses seen with market-leading therapies.

For comparison, established treatments like Vabysmo have reported average gains of around 5 letters at one month, while studies for Lucentis showed an average one-line (5-letter) improvement in treatment-naïve patients. While early and from a small patient group, TH103's 10-letter gain after a single injection suggests a potent and rapid effect on vision recovery.

Anatomically, the drug also demonstrated robust activity. Patients saw a mean reduction of 129 micrometers (μm) in central subfield thickness (CST), a key indicator of retinal swelling and disease activity. This compares favorably to the reductions seen with other anti-VEGF agents in their initial treatment phases. Furthermore, a near-total reduction of approximately 95% in intraretinal fluid was observed, indicating that TH103 is effectively drying the retina and halting the damaging leakage characteristic of nAMD.

"These initial Phase 1a data are highly encouraging and validate the molecular engineering approach we pursued in developing TH103," said Dr. Napoleone Ferrara, the company's scientific co-founder and a pioneer whose research led to the entire class of anti-VEGF therapies. "We believe the rapid visual and anatomic improvements we observed are consistent with potent VEGF inhibition."

A New Chapter in Treatment Durability?

Beyond its immediate efficacy, the most significant potential of TH103 may lie in its durability. The primary challenge with current nAMD treatments is the need for frequent injections, often monthly or every two months, which creates a substantial burden for patients and their caregivers. This can lead to missed appointments, treatment fatigue, and ultimately, suboptimal vision outcomes.

Kalaris reported that following just a single injection of TH103, nearly a third of patients (31%) did not require any additional anti-VEGF treatment for the entire six-month follow-up period. This early signal of extended duration is the core of the drug's promise. If these results can be replicated after a standard series of initial loading doses in larger trials, TH103 could offer treatment intervals of six months or longer, a game-changer for patient quality of life.

The scientific basis for this potential durability comes from the drug's unique design. Invented by Dr. Ferrara, TH103 was specifically engineered to remain in the eye longer. Pharmacokinetic analysis from the trial supports this hypothesis, showing that the maximum concentration of TH103 in the bloodstream was 27 to 51 times lower than that of leading competitors. This suggests the drug is staying localized within the eye to exert its effect, rather than clearing quickly into the systemic circulation.

"The pharmacokinetic profile and retreatment data provide early signals that the enhanced intraocular retention designed into the molecule may translate to extended clinical durability and reduce the treatment burden for patients," said Andrew Oxtoby, Chief Executive Officer of Kalaris.

Navigating a Competitive Market

TH103 enters a fiercely competitive nAMD market dominated by blockbuster drugs like Regeneron's Eylea and Roche's Vabysmo. The battleground in recent years has shifted decisively toward durability, with newer therapies like Eylea HD and Vabysmo already offering patients the ability to extend dosing intervals to three or four months. TH103's early data suggests it could compete directly on this crucial metric, potentially disrupting the established hierarchy if its promise holds in later-stage trials.

The involvement of Dr. Ferrara lends significant credibility to the program. His foundational work on VEGF inhibition underpins the entire multi-billion dollar market for these drugs, and his direct hand in designing TH103 for enhanced retention provides a compelling scientific narrative that resonates with clinicians and investors alike.

Kalaris also demonstrated a proactive approach to safety. The trial noted two cases of transient, mild-to-moderate intraocular inflammation at the highest dose. The company quickly traced the issue to host cell proteins in the drug product and implemented additional purification steps in its manufacturing process. Subsequently, six more patients were treated with the newly purified drug at the same dose level, with no new cases of inflammation observed. This swift resolution of a potential safety concern is a positive indicator of the company's manufacturing control and responsiveness, a key factor for future regulatory review.

Based on the strength of these initial findings, Kalaris is accelerating enrollment in its ongoing Phase 1b/2 study. This larger, dose-finding trial will evaluate TH103 after a standard four-dose monthly loading regimen to identify the optimal dose for pivotal Phase 3 studies. The company expects to share preliminary data from this next crucial study in the second half of 2026, which will provide a clearer picture of whether TH103 can truly redefine the standard of care for patients with nAMD.