Kaleido Biosciences (Kaleido) is a clinical-stage biotechnology company with 82 employees headquartered in Bedford, Massachusetts. Founded in 2015 by Geoffery von Maltzahn and Noubar Afeyan, it is a leading developer of microbiome-therapeutics that leverages a differentiated chemistry-based approach to modify the metabolic output and profile of the microbiome. Modulating the microbiome is significant to human health as a number of disease states (autoimmune disease, metabolic syndrome, diabetes, etc) are inherently tied to the function of the microbiome.
The company has raised private funding totaling $165.5M prior to IPO (Initial Public Offering), and is now listed on the market (NASDAQ: KLDO). Kaleido's Microbiome Metabolic Therapies (MMT™) distinguishes it from companies such as Evelo Biosciences (NASDAQ: EVLO) and Seres Therapeutics (NASDAQ: MCRB) that operate in the microbiome-therapeutics space. The MMT™ platform utilizes a library of 1,500+ synthetic glycans that are orally administered, have limited systemic exposure, and are selectively metabolized by enzymes in the microbiome. This is in contrast to approaches that administer live bacteria contained in oral capsules to modify microbiome function and exert a systemic therapeutic impact.
Kaleido's MMT platform is based on scientific evidence that 86% of human blood metabolites are derived from microbial metabolic pathways, and about 300 unique blood metabolites (46%) are associated with the gut microbiome . This suggests that the gut microbiota is a sink of the majority of metabolites. An example where the gut microbiome can be modified to treat disease conditions is in people with urea cycle disorder (UCD), a genetic disease caused by deficiency in enzymes that constitute the urea cycle. UCD can result in ammonia accumulation in the brain, causing irreversible brain damage and possible death. A significant proportion of ammonia is produced by the gut microbiome, thus Kaleido leverages its MMT platform to reduce net ammonia production by modulating the metabolic output and profile of the microbiome.
Kaleido's discovery and development model begins with ex vivo screening of MMT chemistry library in healthy microbiome samples or patient microbiome samples and validating in animal models of the disease, where informative. This is followed by rapid advancement into human clinical studies that 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, an Investigational New Drug (IND) or regulatory equivalent outside the US will be filed and development will proceed to Phase 2 or later stage clinical trials. Time to Phase 2 trials for one of the MMT candidates is about 2 years after the first ex vivo screening, indicating a rapid advancement model.
Kaleido's current MMT candidates encompass diverse indication areas including urea cycle disorders, hepatic encephalopathy, pathogenic infection, ulcerative colitis, immuno-oncology, and metabolic health . As of October 2020, Kaleido has clinical development pipelines consisting of phase 2 clinical trial in urea cycle disorder, phase 1 clinical trial in ulcerative colitis, and phase 1/2 clinical trial in mild COVID-19.
Kaleido's clinical trial pipelines are expected to be doubled in 2021, as the company plans to initiate phase 2 clinical studies on hepatic encephalopathy and Inflammatory bowel diseases. Kaleido is also advancing the preclinical MMT candidates targeting liver disease, atopic dermatitis, Clostridium difficile infection (CDI), immuno-oncology.
Furthermore, Kaleido has been expanding the global IP portfolio on the MMT platform very aggressively with more than 100 patents currently being reviewed or pending for application in addition to the company's current patents (9 in the US and 2 in Europe).
Despite the short history of the company, Kaleido has successfully established a unique niche within the rapidly growing microbiome therapeutics industry with their MMT platform and expected to grow significantly in the next few years.
1. Visconti, A., Le Roy, C.I., Rosa, F. et al. Interplay between the human gut microbiome and host metabolism. Nat Commun 10, 4505 (2019).
2. Kaleido Biosciences: Corporate Overview Presentation - October 2020 (https://investors.kaleido.com/events-presentations)