Kaleido Biosciences presents Microbiome Metabolic Therapy data at ILC

Kaleido Biosciences presented clinical study and ex vivo data supporting its Microbiome Metabolic Therapy, or MMT, programs in diseases resulting in hyperammonemia at The International Liver Congress, or ILC. The gut microbiome plays a significant role in the production and consumption of ammonia, which is central to the pathogenesis of several ammonia processing-related diseases. Kaleido is currently advancing novel MMT product candidates, KB195 and KB174, targeted at reducing net ammonia production by modulating the metabolic output and profile of the microbiome. In an ex vivo screening of more than 300 compounds across healthy human microbiome samples, KB195 showed an effect on ammonia reduction. In ex vivo testing, KB195 reduced ammonia levels in 95% of microbiome samples from patients with hepatic impairment. In 74% of the samples, KB195 also resulted in a greater reduction in ammonia than lactulose, an approved treatment for hepatic encephalopathy. The safety and tolerability of KB195 and its effect on microbiome nitrogen metabolism were subsequently evaluated in a randomized, controlled, double-blind, non-Investigational new drug, or non-IND, clinical study in healthy human subjects. The study enrolled 47 subjects, who were administered a high-protein diet and randomized to receive either KB195, a comparator glycan, or negative control, and the dose was escalated during 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 is consistent with a reduction in net ammonia production by the gut microbiome. The KB195 group had a decrease of 40.5% in urinary 15N excretion compared to negative control at a dose of 36g twice daily (72g/day), independent of starting microbiome composition. Overall, there were no safety signals following KB195 treatment. Most treatment-emergent adverse events during the study were mild in severity. Of the two subjects who reported, none were deemed related to KB195. Tolerability was evaluated using the gastrointestinal tolerability questionnaire, which assesses symptoms like flatulence and abdominal cramping, and the Bristol Stool Scale, which assesses stool consistency. KB195 was well tolerated and comparable to the negative control at all doses in both the GITQ and BSS. Treatment with KB195 also resulted in fewer subjects reporting diarrhea than with the comparator glycan.

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