The goal of the proposed project is to evaluate the potential of and develop HBI-201, a novel oral formulation of nitrous oxide (N2O), that enables the home use of N2O to treat pain associated with Vaso-Occlusive Crises (VOCs) in Sickle Cell Disease (SCD). The analgesic properties of N2O are well known, and N2O is an FDA- designated medical gas that is used for its analgesic, among other, properties. Importantly, current analgesic uses of N2O using inhaled gas include pain from SCD VOC in the emergency department (ED) in France, as well as in obstetric labor, acutely painful procedures such as fracture reduction, and in the management of the pain of ureteric colic. As a widely used, approved drug in the US, EU, and other geographies, the safety, tolerability, and efficacy of inhaled N2O (iN2O) has been demonstrated. However, barriers to home dosing of iN2O have prevented the development of an N2O therapeutic for home treatment of SCD VOC pain. Inhaled N2O gas is the approved modality for N2O. However, inhaled N2O is not a viable therapeutic option for home use due to poor dosing control, potential inhalation equipment issues and variability in patient ventilation and pulmonary absorption, the risk of inadvertent exposure due to leaking or incorrectly operated compressed gas cylinders, and patient resistance to gas therapies due to issues with mask and cannula use. HBI-201, a novel oral N2O drug product, enables home use of N2O in SCD and is being developed for the treatment of pain associated with VOCs in SCD. The administration of a defined dose of N2O delivered by oral administration of HBI-201 enables the further development of N2O as a therapeutic for home use while obviating the problems associated with iN2O. In this multi-PI application, we combine the expertise of the Simone and Belcher laboratories with Hillhurst’s experienced team and innovative technology and propose to build on compelling data to develop HBI-201 as a treatment for SCD VOC pain.

This application aims to investigate and develop HBI-201, an oral nitrous oxide (N2O) therapeutic, for the treatment of acute pain associated with vaso-occlusive crises (VOC) in sickle cell disease (SCD) patients. This project will evaluate whether HBI-201 has an appropriate preclinical efficacy and toxicologic profile for further development in SCD, and also evaluate the clinical safety, tolerability, pharmacokinetic and pharmacodynamic profile of HBI-201 in normal healthy volunteers. If successful, this research will provide critical safety, dosing, and preclinical efficacy information for advancing HBI-201 into a Phase 2 clinical trial in SCD patients, with the ultimate objective being to provide a non-opioid therapeutic for home use to treat the severely painful VOC episodes of SCD patients, thus reducing the pain experienced by patients, the need for opioid-based therapy, and the need for patients to present to emergency departments and hospitals.