Sickle cell disease (SCD) is a devastating condition that is widely recognized for its hallmark pain crisis or vaso- occlusive events (VOE). There is currently a lack of effective disease-modifying therapies for VOE once it has begun, and pain management with opioids remains the standard of care in attempt to mask the debilitating pain. Combined with the ongoing opioid crisis, this has led to SCD patients being treated as ‘drug-seekers’ when seeking medical care, thus eroding confidence in the healthcare system, and leaving individuals with SCD to attempt to manage VOE on their own. Furthermore, numerous VOEs and prolonged opioid use lead to daily chronic pain in over 50% of adults with SCD. The resulting impact of acute and chronic pain on individuals with SCD is profound and is reflected in burden of disease statistics where SCD burden exceeds Alzheimer’s disease, breast and colorectal cancer, HIV/AIDS, leukemia, and stroke. An effective disease-modifying treatment for VOE that addresses its complex underlying path mechanisms that lead to pain is urgently needed. We are therefore developing IHP-102, a disease-modifying treatment for at-home self-management of VOE, thus empowering patients and providing significant freedom from disease. IHP-102 is a novel glycan-based therapeutic with pleiotropic activity that targets multiple path mechanisms of VOE, including P-selectin and complement. Addressing structural barriers is critical for true patient impact; therefore, IHP-102 is intended for home-based self-administration at the earliest onset of VOE symptoms, thus circumventing the largely ill-equipped healthcare system. This treatment profile incorporates direct feedback from the SCD community and would represent a major paradigm shift that would revolutionize SCD care and provide significant burden from disease. We have shown that IHP-102 inhibits P-selectin mediated cell binding, inhibits complement-mediated cell lysis, and reduces vaso-occlusions by 75% in the Townes SCD mouse model of VOE. IHP-102 is highly differentiated from other SCD drugs approved or in development, both with its pleiotropic biological activity and in its home- based treatment paradigm. In the proposed work, we will utilize SCD pain models to build robustness to the therapeutic potential and clinical translation of IHP-102. We will also scale up to GMP manufacturing and perform IND enabling studies, resulting in a first-in-human Phase 1 clinical trial. Successful completion of the aims proposed here will significantly advance the clinical development of IHP-102 and help to realize its potential to holistically address VOE as a non-opioid approach to alleviate pain, duration, and associated complications.

Current therapies for sickle cell disease largely fail to meet patient needs, especially for the management of acute pain crisis associated with this devastating disease. With opioids as the primary treatment option for masking pain, the SCD community regularly describes being treated as ‘drug-seekers’ while in the midst of these extremely painful and life-threatening events, leaving no option but to attempt to manage symptoms at home. We are therefore developing IHP-102, a novel therapeutic that targets multiple mechanisms of pain crisis, for at- home self-management of pain crisis, which would represent a revolutionary shift in SCD treatment that empowers patients and provide significant freedom from disease.