Successful completion of Autoimmune Program with Ginkgo Bioworks

Microba Life Sciences today announced that all screening activities for our Autoimmune Disease Program with partner Ginkgo Bioworks (NYSE: DNA) have been completed on schedule. From more than three million data points generated, six therapeutic leads with compelling disease-relevant activity have been selected for further pre-clinical development. The screening identified leads that exerted potent immunomodulatory effects in multiple disease-relevant cell types.

Professor Trent Munro, SVP Therapeutics at Microba said: “Microba is at the forefront of developing precision microbiome therapeutics, enabled by machine learning and artificial intelligence, that have the potential to help patients in need across a number of disease indications. Over the past two years, we have broken new technical ground with this project and probed frontier biology imparted by novel microbes derived from the human microbiome. This approach has now allowed selection of potent lead candidates that will be progressed as therapeutics. Autoimmune diseases represent a significant unmet need and the identification of potential live biotherapeutics is an exciting development in the creation of new modalities to improve the lives of these patients.”

Next steps for this program are to assess therapeutic efficacy of these six lead strains in disease-relevant animal models and manufacturing for clinical trials.

Autoimmune Disease Program and Ginkgo Bioworks Partnership

The goal of this program was to discover and develop novel treatments for autoimmune diseases such as lupus, psoriatic arthritis and certain autoimmune liver diseases.

• In mid-2022 Microba commenced its autoimmune disease therapeutic program in partnership with Ginkgo Bioworks
• Microba first used its proprietary databank and advanced machine learning analytics to identify ~200 diverse gut microbiome bacterial species as therapeutic leads for targeting autoimmune diseases
• Ginkgo then screened these leads for immunomodulatory activities based on a co-designed, bioanalytical assay screening cascade.

In Stage 1:

• 182¹ bacterial strains selected through Microba’s data-driven drug discovery platform were screened across an array of primary in vitro screening assays for disease-relevant biological activity
• The results demonstrated that 80% of strains exhibited activity in one or more primary screen assay, 62% demonstrated significant immunomodulatory activity, and 18% demonstrated significant inflammasome activity
• 36 strains were selected and progressed into Stage 2 functional screening.

In Stage 2:

• Screening of the 36 down-selected strains was performed in disease-relevant human cells including gut epithelial, liver fibroblast, synovial (joint connective) tissue, and primary immune cells (directed at specific cell pathways and targets of relevance to autoimmune disease)
• Mechanism of action of select leads was characterised by multi-omics approaches including by transcriptomic analyses of host cells and secretome metabolomic analyses of lead strains.

The final data package enabled down-selection to six strains that demonstrate compelling disease-relevant activity for a range of autoimmune disorders.

Autoimmune diseases are a family of more than 80 chronic and often life-threatening illnesses, which occur when the body’s own immune system attacks the body’s healthy cells, tissues and organs. Autoimmune conditions now impact around 5% of the population and their prevalence is rising² . In recent years, several studies have highlighted the role of the microbiome in the pathogenesis of autoimmune diseases³.

Therapeutic Platform & Programs

There is a growing body of evidence that the gut microbiome plays a central role in the maintenance of health and the development of chronic disease. With microbiome-based therapeutics in clinical development and the first FDA approvals, these novel drugs represent an exciting new opportunity for the treatment of chronic diseases that are undeservedly by current pharmaceuticals.

Microba is at the forefront of this field using its advanced proprietary metagenomics technology developed by leading Australian researchers in the top 1% of cited researchers globally. Using this technology, Microba has established a data-driven platform for drug discovery and development from the human gut microbiome. This platform leverages a large, growing, proprietary databank and is generating multiple potent therapeutic candidates to address chronic diseases. Microba has established three therapeutic programs spanning Inflammatory Bowel Disease (IBD), Immuno-Oncology and Autoimmune Diseases, with lead candidate MAP 315 under the Company’s IBD program the first program to enter human clinical trials.

References

1. 200 strains selected through Microba’s data driven drug discovery platform were transferred to Ginkgo Bioworks of which 18 did not meet the growth specifications resulting in 182 strains progressing through primary screens
2. Fugger, L.et al. Challenges, Progress, and Prospects of Developing Therapies to Treat Autoimmune Diseases. Cell. (2020).
   https://doi.org/10.1016/j.cell.2020.03.007https://doi.org/10.1016/j.cell.2020.03.007.
3. De Luca, F. and Shoenfeld, Y. The microbiome in autoimmune diseases. Clin Exp Immunol. (2019). https://doi.org/10.1111/cei.13158.