ILX002 (Hemoglobin S Polymerization Inhibitor)
ILX002 was discovered by Illexcor Therapeutics in collaboration with scientists from Virginia Commonwealth University, Children’s Hospital of Philadelphia, and King Abdulaziz University (Saudi Arabia).
Mechanism of Action
ILX002 is the first drug candidate that inhibits polymerization by directly binding to and disrupting interactions between Hemoglobin S molecules. ILX002 rapidly partitions into red blood cells and engages with and fundamentally disrupts important secondary intermolecular contacts that stabilize interactions between Hemoglobin S molecules. ILX002 is distributed pancellularly to inhibit Hemoglobin S polymerization in essentially all circulating red blood cells. The goal is to restore normal blood rheology and prolong red blood cell survival to prevent the pathophysiology of the disease.
Efficacy
ILX002 is the most potent Hemoglobin S polymerization inhibitor discovered to date. ILX002 exhibits sustained inhibition of red blood cell sickling in vitro for greater than two hours even in total anoxic conditions. Voxelotor, the only FDA approved Hemoglobin S polymerization inhibitor, does not demonstrate any direct inhibition of polymerization and cannot sustain inhibition of red blood cell sickling.
Townes mice express humanized mutant βS-globin and clinically reproduce sickle cell disease sequalae, with severe anemia, hemolysis,
and inflammation. When administered to Townes mice, ILX002 demonstrated unprecedented reversal of the disease pathophysiology, with
dramatic reductions in anemia and reticulocytosis, hemolysis, and inflammation.
1. Restored normal hemoglobin levels
2. Reticulocytes reduced from about 50% at baseline to less than 20%
3. 60% reduction in bilirubinemia
4. 85% reduction in neutrophil count
If these results are reproduced in human patients with sickle cell disease, ILX002 would be the first oral therapy that provides clinical benefits
that meet or exceed those of ex vivo gene therapies. ILX002 has the potential to become the drug therapy that clinicians and patients
alike have been searching for over the past few decades.
Safety
ILX002 has demonstrated excellent safety in non-clinical toxicology in rat and dog species.
