Unlimited Bio has opened recruitment for CALM-AF-AI, a Phase 1/2a clinical trial now registered on ClinicalTrials.gov as NCT07443826. The study is designed to evaluate the safety and preliminary efficacy of AAV9-Follistatin gene therapy, both as a standalone treatment and in combination with VEGF plasmid gene therapy, in adults experiencing age-related muscle decline.
CALM-AF-AI is believed to be the first registered clinical study worldwide to combine these two gene therapy approaches in a single protocol. The program is built around a straightforward therapeutic rationale: support muscle growth while also improving the vascular environment needed to sustain it. Follistatin acts by inhibiting myostatin, a natural regulator that limits muscle growth, while VEGF is intended to promote capillary formation and improve delivery of oxygen and nutrients to muscle tissue.
The trial is an open-label, sequential dose-escalation study expected to enroll approximately 12 eligible adults between the ages of 45 and 75. GARM in Roatan is the designated study site where eligible participants will complete in-person study visits and protocol-required procedures under clinical supervision. The protocol uses a 3+3 design across three cohorts, beginning with low-dose AAV-Follistatin monotherapy, followed by high-dose monotherapy, and then a combination arm that adds 4.8 mg of VEGF plasmid. Rapamycin will be co-administered for approximately two months to help mitigate immune responses.
In addition to primary safety endpoints, the study will collect a broad set of exploratory functional and biomarker outcomes over 12 months. These include DXA-measured lean mass, bone mineral density, leg press 1RM, grip strength, VO₂max, six-minute walk distance, frailty scales, and serum follistatin, myostatin, and IGF-1 levels.
The opening of recruitment marks an important step for Unlimited Bio as the company advances a more integrated approach to addressing age-related decline. Data from CALM-AF-AI are expected to inform future development decisions and help build the clinical foundation for combination gene therapy strategies in muscle health and longevity.