Genie:S: on-demand sulfide synthesis and delivery platform technology for ischemia therapy

The National Center for Advancing Translational Sciences awarded Exhalix, LLC $350,000 on September 16, 2025, under the NCATS Project Grant program (CFDA 93.350) to develop and demonstrate the GENIE:S platform technology for on-demand hydrogen sulfide synthesis and targeted delivery to treat peripheral artery disease and chronic limb-threatening ischemia. The platform addresses a clinical gap in precision H2S therapy by enabling local, regional synthesis and controlled dosing of hydrogen sulfide to ischemic tissue, reducing safety concerns and off-target effects that have impeded clinical translation of systemic H2S donor therapies.

The award funds preclinical research conducted through a collaboration between Exhalix and the University of New Mexico School of Medicine. Work is performed in New Mexico with a period of performance from September 16, 2025, through September 15, 2027. Hydrogen sulfide is an endogenous signaling molecule that drives angiogenesis and vasodilation through nitric oxide and HIF-1/VEGF-A pathways; deficiency in endogenous H2S correlates with endothelial dysfunction and microvascular disease. The GENIE:S platform targets delivery of exogenous H2S to regenerate ischemic tissue in PAD and chronic limb-threatening ischemia populations, where current outcomes include 25 percent limb loss and 25 percent mortality within one year.

Abstract

Peripheral artery disease (pad) is a vascular insufficiency problem that affects more than 20 million or nearly 7% of the U.S. Population. Nearly 1 in 10 pad patients eventually develop chronic limb threatening ischemia (CLTI) with a combined annual cost of $21B. Pad is caused by sustained endothelial dysfunction, which is a vascular disorder prevalent among smokers and diabetics, and IT is often missed until the symptoms become advanced enough to lead to CLTI. The resulting lower extremity ischemia in CLTI patients is associated with 25% limb loss and 25% mortality at the end of year 1. Hydrogen sulfide (H2S) is an endogenous gasotransmitter and signaling molecule synthesized by the endothelial layer. In addition to vasodilatory role, H2S is responsible for angiogenesis in endothelial cells through activation of pathways that include nitric oxide signaling and the canonical HIF-1 and vegf-a-mediated angiogenesis cascade. There is also significant evidence linking deficiency in endogenous H2S to endothelial dysfunction and consequently microvascular disorder and poor perfusion. Systemic administration of (EXOGENOUS) H2S donors has been shown to markedly improve the rate of regeneration in ischemic tissue. However, widespread clinical translation of systemic H2S therapy is stymied by significant concern over its safe use and unintended off-target effects due to a lack of control and knowledge over the dosage during treatment. This leaves a significant opportunity for a disruptive approach for targeted, precision delivery of H2S to facilitate clinical translation of H2S therapy. The proposed preclinical sbir study, which is a collaboration between exhalix and the university of new mexico school of medicine, will demonstrate the unique platform technology, genie:S, that local- regionally synthesizes and delivers a controlled amount of H2S for a variety of topical clinical applications. We anticipate that the proposed feasibility study will last 12 months and success in reaching our objectives will lead to a phase II effort for the development of advanced prototypes and pre-clinical studies on small and large animals.