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 UCD. We have conducted a non-IND clinical study of KB195 in healthy volunteers and have a non-IND clinical study in UCD patients underway. We also have a cleared IND for KB195 in UCD and have initiated a Phase 2 clinical trial.
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 in 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 have two non-IND human clinical studies to support our HE program underway, including one in patients with well-compensated cirrhosis. We plan to be ready to advance one of these two MMT candidates into a Phase 2 clinical trial for HE 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 have initiated a clinical study of KB109 in patients colonized with MDR pathogens.
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 in immuno-oncology and cardiometabolic and liver diseases.
*Our human clinical studies of our MMT candidates are conducted under regulations supporting research with food, evaluating safety, tolerability and potential markers of effect. For MMT candidates that are further developed as therapeutics, Kaleido conducts clinical trials under an Investigational New Drug (IND) or regulatory equivalent outside the U.S., and in Phase 2 or later development; for those that we elect to continue on a non-drug development pathway, INDs or regulatory equivalent outside the U.S. will not be required.