ILX-002 (Hemoglobin S Polymerization Inhibitor)
ILX-002 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
ILX-002 is the first drug candidate that inhibits polymerization by directly binding to and disrupting interactions between Hemoglobin S molecules. ILX-002 rapidly partitions into red blood cells and engages with and fundamentally disrupts important secondary intermolecular contacts that stabilize interactions between Hemoglobin S molecules. ILX-002 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
ILX-002 is the most potent Hemoglobin S polymerization inhibitor discovered to date. ILX-002 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, ILX-002 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, ILX-002 would be the first oral therapy that provides clinical benefits
that meet or exceed those of ex vivo gene therapies. ILX-002 has the potential to become the drug therapy that clinicians and patients
alike have been searching for over the past few decades.
Safety
ILX-002 has demonstrated excellent safety with repeat dosing in non-clinical toxicology at levels up to 3-fold above the anticipated therapeutic level. Complete non-clinical toxicology and safety pharmacology assessments are ongoing as part of the IND program for the drug candidate.
