Cellio Therapeutics has opened a first-in-human Phase I trial of C.001, an autologous iPSC-derived retinal pigment epithelium cell therapy, in adults with RPE-mediated maculopathy. The move marks the clinical entry of a platform developed over multiple years at UCLA's Jules Stein Eye Institute with backing from the California Institute for Regenerative Medicine (CIRM).
Trial design and the C.001 retinal degeneration program
The Phase I study (NCT07594236) is a single-center, open-label, dose-escalation trial enrolling approximately 15 adults with conditions characterized by RPE degeneration, including geographic atrophy, Stargardt disease, and age-related macular degeneration. Participants receive a single subretinal injection of C.001 across three sequential dose cohorts — low, medium, and high — with a sentinel dosing strategy and mandatory four-week observation windows between escalations. An independent Data Safety Monitoring Board reviews safety data before each escalation step. The primary endpoint captures the incidence of ocular and systemic adverse events over three months, with secondary measures including change in visual acuity assessed by ETDRS letter score and anatomical changes on optical coherence tomography. Participants are followed for up to 12 months. The trial began recruiting in April 2026 at a Beverly Hills, California site, with primary completion expected by the end of 2028, according to the trial record.
The design reflects the particular caution warranted when delivering living cells into the subretinal space — a surgically sensitive compartment where immune privilege is meaningful but not absolute, and where any adverse engraftment event could cause irreversible photoreceptor damage. The sentinel approach, combined with DSMB oversight, is consistent with regulatory expectations for first-in-human cell therapy trials in ocular indications.
Biological rationale for RPE mediated maculopathy therapy
The RPE is a monolayer of pigmented epithelial cells situated between the photoreceptors and the choroidal vasculature, performing functions essential to photoreceptor survival: recycling visual cycle retinoids, phagocytosing shed photoreceptor outer segments, and maintaining the outer blood-retinal barrier. In geographic atrophy — the advanced dry form of AMD — and in Stargardt disease, a hereditary macular dystrophy caused by mutations in the ABCA4 gene, progressive RPE cell death precedes and drives photoreceptor loss, ultimately producing irreversible central vision impairment. No approved therapy halts or reverses RPE atrophy in either condition beyond the complement inhibitors pegcetacoplan (Syfovre, Apellis) and avacincaptad pegol (Izervay, Astellas), which slow but do not stop geographic atrophy progression and have no established role in Stargardt disease.
C.001 takes a cellular replacement approach: RPE cells are derived from the patient's own induced pluripotent stem cells, which are themselves generated by reprogramming somatic cells — most likely skin-derived fibroblasts, based on the published UCLA platform description — before directed differentiation into RPE. The autologous origin is designed to reduce the immunological barriers that have complicated allogeneic cell transplantation in the eye, even within its relatively immune-privileged environment. According to the CIRM award page for Cellio Therapeutics, CIRM awarded $7.9 million under grant CLIN2-19416 to support the clinical trial stage of this program.