Developing a topical beta blocker formulation as a targeted therapeutic for infantile hemangioma

/ ABSTRACT This application is responsive to the stated goals of the NHLBI Branch: to understand and promote health and resilience and enable the translation of discoveries from basic science into clinical practices. Arkayli Biopharma is developing a novel topical therapeutic for infantile hemangioma (IH) formulated for superior efficacy, safety, and convenience compared to the solitary FDA-approved oral treatment. Infantile hemangioma (IH) is a blood vessel tumor that affects around 170,000 infants annually in the United States. These benign vascular tumors are barely evident at birth but grow rapidly in the first few weeks-months of life and can interfere with breathing and vision, however, the most common complications are ulceration and permanent scarring. Infantile hemangiomas are composed of proliferating endothelial-like cells, and treatment is aimed at inhibiting vascular proliferation before complications arise. Although oral β blockers have become a standard first-line therapy for IH, there remains a crucial need to enhance safety by reducing systemic exposure to β blocking agents. Some physicians and parents hesitate to start β blockers because of the known (respiratory, metabolic, and cardiovascular) and unknown long-term risks related to neurocognitive function. Our novel formulation leverages soft drug design to create a safer medication with an enhanced therapeutic index by incorporating metabolism considerations into the drug design process. Given the systemic drug exposure associated with administration of both oral and topical β blockers, our goal is to address this challenge by developing a topical formulation that undergoes rapid metabolism in the blood, within minutes after leaving the skin. Consequently, this formulation will result in negligible accumulation of active drug in the blood and minimal systemic β-adrenergic antagonism, making it safer than existing products on the market. By combining a high local concentration of the active agent with low systemic exposure, our product will maximize therapeutic efficacy while minimizing adverse cardiovascular, metabolic, respiratory, and neurological effects in young infants. We have robust in-vitro data validating our hypothesis, and preliminary animal studies demonstrating no systemic β-adrenergic antagonism when our product is applied topically. In this Phase I project, Arkayli Biopharma will partner with the University of Wisconsin to complete pivotal research and development studies needed to submit an Investigational New Drug Application. Aim 1: Evaluate the effects of ARK 001 formulation on in-vitro endothelial cell tube formation, proliferation, and invasion. Aim 2: Conduct enabling nonclinical animal pharmacokinetic and toxicity studies. The outcomes of this research will inform study design and dose selection for the definitive Good Laboratory Practices (GLP) toxicology study in juvenile animals. The long-term overarching goal is to address a significant unmet commercial demand by creating a novel formulation of a topical treatment for infantile hemangiomas (IH). This formulation will be highly effective, user-friendly, and notably safer than existing products on the market. Project Number: 1R41HL177866-01A1 | Fiscal Year: 2025 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: Seth Reno | Institution: ARKAYLI BIOPHARMA, INC., MOUNT AIRY, MD | Award Amount: $306,804 | Activity Code: R41 | Study Section: Special Emphasis Panel[ZRG1 IVBH-V (11)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R41HL17786601A1