Kaleido is currently advancing MMTs that target hyperammonemia, a metabolic condition generally characterized by elevated levels of ammonia in the blood. Our hyperammonemia programs are focused on two specific diseases, urea cycle disorders (UCD) and hepatic encephalopathy (HE).
Urea Cycle Disorders (UCD)
UCD is a serious and life-threatening inherited, rare genetic disease caused by a deficiency in one of the six enzymes or two amino acid transporters that constitute the urea cycle. UCD can lead to hyperammonemia. Hyperammonemic crises can be fatal and may be precipitated by routine childhood illnesses or any other stress, such as surgery, that causes the body to break down protein. Although UCD encompasses eight distinct mutations, the symptoms and treatments across the subtypes are largely similar. The estimated incidence of UCD is 1 in 35,000 live births in the United States and Europe. UCD is diagnosed either through newborn screening, or at a later point when symptoms of the disease present.
KB195 is our lead MMT candidate in development for the treatment of hyperammonemia in patients with UCD. We have conducted a non-IND human clinical study with KB195 in healthy volunteers and have initiated a non-IND human clinical study in UCD patients. We also have a cleared IND for KB195 in UCD that allows us to advance directly into a Phase 2 clinical trial which we expect to initiate in the first half of 2019.
Hepatic Encephalopathy (HE)
HE describes a spectrum of potentially reversible neurologic and psychiatric abnormalities generally seen in patients with liver failure. HE is a common complication of all forms of cirrhosis, and up to 80% of cirrhotic patients have some form of HE, ranging from minimal hepatic encephalopathy, or MHE, to overt hepatic encephalopathy, or OHE. In the United States alone, it is estimated that over 500,000 patients suffer from some form of HE, not all of whom have been diagnosed. Patients with cirrhosis have an increased risk of developing bacterial infections, and infection is a common precipitant of HE, as well as an independent predictor of mortality in these patients.
We are evaluating both KB195 and KB174 for clinical development for the potential treatment of HE. For KB195, data from our hyperammonemia program in UCD will inform our decision as to whether to develop KB195 in HE. For KB174, we plan to initiate two non-IND human clinical studies in the first half of 2019 to support our HE program, including one in patients with hepatic impairment. We plan to be ready to advance one of these two MMT candidates into a Phase 2 clinical trial for OHE under an IND, if the IND is cleared, in the second half of 2020.
Infections Caused by Multi-Drug Resistant (MDR) Bacteria
MDR pathogens are a significant and growing global health threat. In the United States alone, at least two million people per year are infected with bacteria resistant to antibiotics. Some patients are at particularly high risk of MDR pathogen colonization and infection, including those who undergo a hematopoietic stem cell transplantation. Bacterial infections are also common in liver transplant recipients, both in the period prior to a liver transplant and post-engraftment. In patients with End Stage Liver Disease, infection rates are as high as 40% in the first year after transplant waiting list placement. Infection is the most common reason patients are removed from the waiting list.
Kaleido is advancing an MMT candidate, KB109, to address infections caused by MDR bacteria, by selectively advantaging certain bacteria that exist in the gut. We expect to initiate a non-IND human clinical study with KB109 in the first half of 2019.
Other Therapeutic Areas
There is broad potential to leverage the Kaleido platform to develop MMTs targeting other therapeutic areas. We are identifying and planning to advance MMT candidates for atherosclerotic cardiovascular disease and chronic kidney disease.