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. It is estimated there are approximately 3,000 patients in U.S. and approximately 4,500 patients in Europe with UCD. 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 completed clinical studies of KB195 in healthy volunteers and in patients with UCD and have an ongoing Phase 2 clinical trial under IND/CTAs in patients with UCD who are inadequately controlled on standard of care.
Hepatic Encephalopathy (HE)
HE describes a spectrum of potentially reversible neurologic and psychiatric abnormalities generally seen in patients with liver disease. HE is a common complication of all forms of cirrhosis, ranging from minimal hepatic encephalopathy, or MHE, to overt hepatic encephalopathy, or OHE. In the U.S. alone, it is estimated that there are up to 500,000 patients with HE, of which more than 100,000 patients have OHE. 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.
Kaleido plans to advance KB174 for HE based on positive top-line results from a clinical study in patients with cirrhosis. Kaleido expects to initiate its next study of KB174 evaluating clinical endpoints in patients with HE during 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, more than 2.8 million antibiotic resistant infections occur each year. 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.