Microbiome Report for Week Ending 1/26/19

Second Genome Doses First Patient In Phase 2 Clinical Study Of SGM-1019 For The Treatment Of Nonalcoholic Steatohepatitis (NASH)
Second Genome, Inc.  announced on 1/23/19 that the first patient has been dosed in a Phase 2 clinical trial evaluating SGM-1019 for the treatment of nonalcoholic steatohepatitis (NASH). SGM-1019 is a first-in-class, oral, small molecule inhibitor of P2X7, a receptor that is involved in inflammasome activation and mediates inflammation and fibrosis.

"There are no approved therapies for NASH at this time, and, while there are many in development, SGM-1019 is directed at the inflammation underlying this condition," said Stephen Harrison, Medical Director of Pinnacle Clinical Research and the study's Principal Investigator. "We know that inhibiting P2X7 results in significant reduction in inflammation and fibrosis in preclinical models of disease and look forward to seeing the data from this study. SGM-1019 has the potential to provide a much needed treatment option for the growing number of patients with NASH."

The Phase 2a randomized, double-blind, placebo-controlled study of SGM-1019 will enroll 100 patients with NASH at leading treatment centers across the United States. The trial (NCT03676231) is designed to evaluate the preliminary safety, tolerability, pharmacokinetics and efficacy (measured by ALT and MRI) of oral twice-daily dosing of SGM-1019 at two different dose levels. Top line data are expected in the first half of 2020.

"The advancement of SGM-1019 represents a significant milestone for the company, as it demonstrates our primary commitment to building a clinical-stage, diversified pipeline of small molecules, peptides, and proteins derived from our novel microbiome-based drug discovery platform," said Karim Dabbagh, president and CEO of Second Genome. "We believe 2019 will be a defining year for Second Genome, with the team, platform, pipeline and vision in place to truly make a difference in the lives of patients. In addition to continuing to advance SGM-1019, we also expect our earlier programs to deliver clinical candidate molecules and early leads in our core indications."

Vedanta Biosciences Publishes Seminal Research in Leading Scientific Journal Regarding its Immuno-oncology Candidate, VE800
The research demonstrates that specific, human microbiome-derived bacteria assembled rationally into consortia can cooperatively enhance the responses to immune checkpoint inhibitors
Based on this research, Vedanta is advancing VE800, a proprietary clinical candidate designed to enhance immune responses against cancer.
Vedanta plans to initiate clinical studies in 2019

Vedanta Biosciences, a clinical-stage company developing a new category of therapies for immune-mediated diseases based on rationally-defined consortia of human microbiome-derived bacteria, announced on 1/23/19 a publication in Nature that revealed a newly discovered mechanism underlying antitumor immunity that involves human microbiota-driven induction of interferon-gamma-producing (IFNy+) CD8+ T cell accumulation in the gut and tumors. Led by Vedanta’s scientific co-founder Kenya Honda, M.D., Ph.D., of Keio University School of Medicine, the research also led to the identification and selection of a defined consortium of human microbiome-derived bacterial strains that harnesses this mechanism of antitumor activity and cooperatively potentiates responses to checkpoint inhibitor therapies and immune challenges in general. Based on this research, Vedanta is advancing VE800, a proprietary clinical candidate designed to enhance immune responses against cancer. Vedanta plans to initiate clinical studies in 2019 to evaluate VE800 in combination with Bristol-Myers Squibb’s checkpoint inhibitor OPDIVO® (nivolumab).

“This research demonstrates that specific, human microbiome-derived bacteria assembled rationally into consortia can cooperatively enhance the responses to immune checkpoint inhibitors, which supports our hypothesis that modulating the gut microbiota could be a powerful tool for potentiating immune responses that help fight cancer and infection,” said Bernat Olle, Ph.D., Chief Executive Officer of Vedanta Biosciences. “This work also builds upon Dr. Honda’s previous groundbreaking research on the role of the human microbiome in modulating a range of immune responses and provides a robust scientific foundation for our proprietary lead cancer candidate, VE800.”

The authors of the Nature paper sought to understand the previously poorly-characterized relationship between the human microbiota and intestinal IFNy+ CD8 T cells, which are critical to innate and adaptive immune responses. In preclinical models, they were able to establish that the number and frequency of these immune cells in the gut depend on the presence of a gut microbiota and are plastic, with specific members of the microbiota promoting their intestinal accumulation in an inducible and reversible manner. The authors went on to identify specific commensal bacterial strains from healthy human donors that spurred the production of IFNy+ CD8+ T cells.

Through rigorous selection, the authors isolated a defined consortium of commensal bacteria derived from the human microbiome that proved most effective at inducing rapid and persistent accumulation of IFNy+ CD8+ T cells. Mice colonized with the defined bacterial consortium demonstrated enhanced therapeutic efficacy in a range of tumor models when given in conjunction with PD-1 or CTLA4 immune checkpoint inhibitors. The strains identified are primarily rare, low-abundance components of the human microbiome, representing a significant opportunity for amplification as a therapeutic strategy.

The research demonstrates for the first time that human microbiome-derived bacterial consortia that cooperatively enhance the responses of immune checkpoint inhibitors can be identified. The authors addressed the challenge of reducing a complex community of human microbiome bacteria down to a few, rationally-defined members that can induce a robust immune potentiation response necessary for an effective cancer immune therapy, and directly linking their activity to pathways that promote antitumor immunity.

The Nature paper also found that human stool samples showed considerable variability in their ability to induce colonic IFNy+ CD8+ T cells. Vedanta’s development process is designed to bypass this variability by using pure, clonal cell banks of well-characterized bacterial strains isolated from healthy humans to produce defined consortia of uniform composition. This eliminates the need to rely on direct sourcing of fecal donor material of inconsistent composition. Vedanta sources bacteria from a vast, extensively characterized collection of 80,000 bacterial isolates obtained from human donors from four continents, which is believed to be the largest collection of human-gut associated bacteria. It then designs high-throughput assays to screen product candidates against a given disease target.

VE800 is Vedanta Biosciences’ proprietary oral immuno-oncology product candidate. It consists of a rationally-defined bacterial consortium that activates cytotoxic CD8+ T cells, a type of white blood cell that is the predominant effector in cancer immunotherapy. In preclinical studies, VE800 has been shown to enhance the ability of these T cells to infiltrate tumors, thereby promoting suppression of tumor growth and enhancing survival. Data also suggest that VE800 may enhance the effects of checkpoint inhibitors. Vedanta is evaluating VE800 alone and in combination with checkpoint inhibitors as a potential treatment for patients with advanced or metastatic cancers. In December 2018, Vedanta entered into a clinical trial collaboration to evaluate Bristol-Myers Squibb's programmed death-1 (PD-1) immune checkpoint inhibitor OPDIVO (nivolumab) in combination with Vedanta’s VE800, in patients with advanced or metastatic cancers. Clinical trials are expected to begin in 2019.




Immune Biotech Closes New Share Issue
ImmuneBiotech AB, announced on 1/24/19 that is has raised approx. $500,000 in in its recently completed financing round. The company said that due to continued interest from investors, it will continue its fundraising into 2019.

A large portion of the financing will be used to commercialize its lead product GutMagnific. GutMagnific is a new probiotic food supplement for Irritable Bowel Syndrome. The company also has plans to fund an investigation into the clinical effect of GutMagnific.