At the 2026 American Society of Retina Specialists (ASRS) annual meeting in Montreal, Jayakrishna Ambati, MD, a founder and board member of Inflammasome Therapeutics, presented 6-month phase 2 results for the company’s kamuvudine-8 (K8), an investigational dual-inflammasome inhibitor being developed for geographic atrophy (GA). The multicenter study enrolled 30 patients with bilateral GA at 9 US centers and evaluated 3 doses of K8 delivered by a sustained-release intravitreal implant.
For this month’s Retina Minute, Michael A. Singer, MD, spoke with Dr. Ambati about the rationale for targeting inflammasomes, the phase 2 findings, and plans for further development.
Michael A. Singer, MD: Let’s start with K8. What is the rationale behind targeting the inflammasome in GA?
Jayakrishna Ambati, MD: GA is a chronic, multifactorial disease. Complement is certainly one of the players, but there are multiple upstream factors, including retrotransposons, iron, amyloid beta, and oxidized lipids. Many approaches to GA have focused on one factor or another.
We wanted to look at something common to these different pathways—a final common pathway that integrates multiple danger signals. Inflammasomes are part of the immune system and respond to many of the signals implicated in GA. K8 is a small molecule designed to inhibit these inflammasome pathways, so the idea is to intervene downstream of multiple potential drivers of the disease.
Dr. Singer: How is K8 delivered to the eye?
Dr. Ambati: We have a proprietary, sustained-release bioerodible implant designed to deliver K8 over approximately 3 months. Because K8 is a small molecule, it can penetrate the retina from the vitreous and reach the photoreceptors and retinal pigment epithelium.
The implant is administered in the office using a preloaded, 24-gauge, thin-wall injector. Anesthesia can be topical or subconjunctival lidocaine, depending on the physician’s preference. The product also does not require refrigeration or a cold chain.
Dr. Singer: Tell us about the phase 2 study design.
Dr. Ambati: We enrolled 30 patients with bilateral GA. The worse-seeing eye was treated with K8, and the untreated fellow eye served as the control. We studied 3 dose cohorts—0.3 mg, 0.7 mg, and 1.05 mg—with 10 patients in each cohort.
Patients received an implant at baseline and another at month 3, with GA measurements obtained at baseline, month 3, and month 6. Each dose cohort was compared with the pooled group of 30 untreated fellow eyes, and the imaging was evaluated by masked readers at an independent reading center.
Dr. Singer: What did you see in terms of GA lesion growth?
Dr. Ambati: All 3 doses reduced the mean rate of GA lesion growth relative to the pooled control eyes. The best-performing dose was 0.7 mg, which showed a 54% lower mean GA growth rate over 6 months.
One of the things that interested us was how quickly the treatment appeared to have an effect. We saw separation in the lesion-growth curves relatively early, suggesting that the biologic effect begins within the first few months.
Dr. Singer: That 54% number attracted a lot of attention. How should retina specialists think about it in relation to currently available treatments?
Dr. Ambati: The magnitude of the effect is encouraging. The 2 approved GA therapies showed reductions in lesion growth of approximately 13% to 14% vs controls over their first 6 months in the studies used for historical comparison. Of course, these are cross-trial comparisons rather than head-to-head data, so they have to be interpreted appropriately.
For us, the important next step is determining whether the magnitude of the K8 effect can be reproduced in a much larger phase 3 program.
Dr. Singer: What about visual function? That has been a major challenge in GA trials.
Dr. Ambati: That was another encouraging aspect of the study. In a prespecified analysis of patients with extrafoveal lesions, the K8-treated eyes showed a covariate-adjusted mean advantage of 4.0 ETDRS letters in best-corrected visual acuity compared with control eyes over 6 months, and that difference was statistically significant.
We have only 30 patients, so these findings need to be confirmed in a larger trial. But seeing a functional signal alongside the structural effect is important. Ultimately, what matters to patients is not simply slowing the enlargement of an atrophic lesion—it is preserving useful vision.
Dr. Singer: And the treatment is designed to be given every 3 months?
Dr. Ambati: Correct. Patients were treated at baseline and again at month 3. The implant itself is bioerodible, so the goal is sustained drug delivery without leaving a permanent device in the eye.
Durability is important in GA because these are patients who may require treatment for years. If we can maintain efficacy with less frequent administration, that could reduce the treatment burden for patients and practices.
Dr. Singer: Efficacy gets attention, but safety is always a major consideration. What did you see over the 6-month trial?
Dr. Ambati: We were very pleased with the safety findings. There were no drug-related serious adverse events or dose-limiting toxicities. We also saw no cases of endophthalmitis, intraocular inflammation, neovascular AMD, retinal vasculitis, or optic neuropathy during the 6-month study.
That is particularly important because GA treatments are being administered to eyes that often still have meaningful visual function. Any therapy in this setting needs not only to demonstrate efficacy but also to have an acceptable safety profile with repeated treatment.
Dr. Singer: Where does the K8 program go from here?
Dr. Ambati: We’re planning a global pivotal program, although the final design will depend on discussions with regulatory authorities. In the United States, we anticipate a 12-month, 3-arm study evaluating 2 doses of K8 against one of the approved GA therapies in a superiority design. Outside the United States, particularly in Europe, we expect to compare K8 with sham because there are currently no approved GA therapies in many of those markets.
Dr. Singer: So the approved therapy would be dosed according to its established regimen, while K8 would remain every 3 months?
Dr. Ambati: Correct. The study would remain masked, so participants would receive sham procedures during months when they are not receiving an active injection.
Dr. Singer: What do you think K8 could ultimately mean for the treatment of GA?
Dr. Ambati: I think we may be entering a new era in which we can aim for more than simply slowing structural progression. The phase 2 data suggest the possibility of a meaningful effect on lesion growth together with a functional benefit.
That has to be confirmed in phase 3. But if we can reproduce both findings while maintaining the safety and durability we saw in this study, I think that could represent an important advance for patients with GA.
Dr. Singer: Jay, I’ve known you for decades and have watched your work in geographic atrophy for many years. It is exciting to see a next-generation approach that may have the potential to deliver on both structure and function. I look forward to seeing where the phase 3 program takes us.
Dr. Ambati: Thank you very much. RP
