Data Demonstrate Safety and Tolerability of Microbiome Metabolic Therapy (MMT™) Candidate KB195 and Potential for Effect on Nitrogen Metabolism, a Biomarker of Ammonia Production
LEXINGTON, Mass., Sept. 03, 2019 (GLOBE NEWSWIRE) -- Kaleido Biosciences, Inc. (KLDO), a clinical-stage healthcare company with a chemistry-driven approach to leveraging the microbiome organ to treat disease and improve human health, today announced data from a clinical study of KB195 in patients with urea cycle disorders (UCD) are being featured in a poster presentation during the Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Symposium in Rotterdam, the Netherlands, September 3-6, 2019.
The gut microbiome plays a significant role in the production and consumption of ammonia, which is central to the pathogenesis of several diseases, including UCD. UCD are a group of serious, life-threatening, rare genetic diseases, which can lead to hyperammonemia, a metabolic condition generally categorized by elevated levels of ammonia in the blood. KB195, a novel Microbiome Metabolic Therapy (MMT™), designed to reduce net ammonia production by modulating the metabolic output and profile of the microbiome, is in development as a potential treatment for UCD.
“This is the first study of KB195 in patients and it is encouraging to see these data support its continued development as a potential treatment for UCD,” said Johannes Häberle, M.D., Senior Metabolic Consultant at the University Children’s Hospital in Zurich and Assistant Professor for Pediatrics at the University of Zurich. “Patients living with UCD are in need of new treatment options that can help them manage their disease, and I am very excited about the promise of targeting the gut microbiome as an innovative approach.”
“We are very pleased to present the first data evaluating an MMT in patients, and to have one of the leading UCD experts conduct this study of KB195,” said Katharine Knobil, M.D., Chief Medical Officer and Head of Research & Development, Kaleido. “We look forward to seeing how the promising results from this small study translate into our ongoing Phase 2 clinical trial.”
Data presented at SSIEM are from an open-label, single-arm, clinical study to evaluate the safety, tolerability and effect of KB195 on measures of nitrogen metabolism in patients with well-controlled UCD. The study was conducted at a single center and enrolled four patients who received KB195 orally for 21 days, while continuing their standard of care.
In the study, no clinically significant safety signals were observed with KB195 and there were no serious treatment-emergent adverse events. KB195 was generally well tolerated based on measures that included the Gastrointestinal Tolerability Questionnaire (GITQ), and the Bristol Stool Scale (BSS, which is a measure of stool consistency). Patients were well-controlled on their standard of care at study entry, and plasma ammonia levels were within the normal range at baseline and remained normal throughout the study.
A lactose-15N-ureide tracer was used to evaluate changes in nitrogen metabolism in the gut. A reduction of this tracer in the urine and an increase of the tracer in the stool are consistent with a reduction in net ammonia production by the gut microbiome. While the study wasn’t designed to demonstrate a significant effect on this biomarker of ammonia production, in evaluable patients, KB195 was associated with a general decrease in urinary 15N excretion and an increase in stool 15N excretion, suggestive of KB195 activity in reducing nitrogen metabolism.
The SSIEM poster entitled, “An Open-Label, Single-Arm Clinical Study to Evaluate Safety and Tolerability of KB195, A Novel Glycan, in Patients with Urea Cycle Disorders,” will be available on Kaleido’s website at https://kaleido.com/platform/#publications.
A global, multi-center, open-label, single arm Phase 2 clinical trial (UNLOCKED) of KB195 is being conducted under an Investigational New Drug (IND) application in the U.S. and approved Clinical Trial Applications (CTAs) in other countries. It is designed to evaluate the efficacy and safety of KB195 in UCD patients with elevated ammonia levels on standard of care. Patients enrolled in UNLOCKED will receive KB195 administered orally for eight weeks in addition to their standard of care, which includes dietary protein restriction and may include treatment with a nitrogen binding therapy.
About Urea Cycle Disorders
Urea cycle disorders (UCD) are a group of serious, life-threatening, rare genetic diseases caused by a deficiency in one of the six enzymes or two amino acid transporters that constitute the urea cycle, resulting in an impaired ability to process ammonia. UCD can lead to hyperammonemia, a metabolic condition generally characterized by elevated levels of ammonia in the blood. 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.
UCD includes mutations involving eight genes, but the symptoms across subtypes are largely similar. UCD is diagnosed either through newborn screening, or at a later point when symptoms of the disease present. The estimated incidence of UCD is 1 in 35,000 live births in the U.S. and Europe.
About Microbiome Metabolic Therapies (MMT™)
Kaleido’s Microbiome Metabolic Therapies, or MMTs, are designed to drive the function and distribution of the microbiome organ’s existing microbes in order to decrease or increase the production of metabolites, or to advantage or disadvantage certain bacteria in the microbiome community. The Company’s initial MMT candidates are targeted glycans that are orally administered, have limited systemic exposure, and are selectively-metabolized by enzymes in the microbiome. Kaleido utilizes its human-centric discovery and development platform to study MMTs in microbiome samples in an ex vivo setting, followed by advancing MMT candidates rapidly into clinical studies in healthy subjects and patients. These human clinical studies 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, the Company conducts clinical trials under an Investigational New Drug (IND) or regulatory equivalent outside the U.S., and in Phase 2 or later development.
About Kaleido Biosciences
Kaleido Biosciences is a clinical-stage healthcare company with a differentiated, chemistry-driven approach to leveraging the microbiome organ to treat disease and improve human health. The Company has built a human-centric proprietary product platform to enable the rapid and cost-efficient discovery and development of novel Microbiome Metabolic Therapies (MMT™). MMTs are designed to modulate the metabolic output and profile of the microbiome by driving the function and distribution of the organ’s existing microbes. Kaleido is advancing a broad pipeline of MMT candidates with the potential to address a variety of diseases and conditions with significant unmet patient needs. To learn more, visit https://kaleido.com/.
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding the therapeutic potential of our MMT candidates, the timing of initiation, completion and reporting of results of our clinical studies and our strategy, business plans and focus. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Examples of forward-looking statements contained in this press release include, among others, statements regarding our continued plans for development of KB195. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, those related to the breadth of our pipeline of product candidates, the strength of our proprietary product platform, the efficiency of our discovery and development approach, the clinical development and safety profile of our MMT candidates and their therapeutic potential, whether and when, if at all, our MMT candidates will receive approval form the U.S. Food and Drug Administration and for which, if any, indications, competition from other biotechnology companies, and other risks identified in our SEC filings, including our most recent Quarterly Report on Form 10-Q, and subsequent filings with the SEC. Any forward-looking statements contained in this press release represent our views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. We explicitly disclaim any obligation to update any forward-looking statements.