Spurred by landmark research projects & findings, powered by significant grant dollars, surging clinical trials, and historic levels of venture funding, the microbiome market is marching towards the mainstream.
Advances in next generation sequencing (NGS), informatics, computing power, gene editing, synthetic biology, and now proteomics and metabolomics has brought about this revolution. The microbiome is a rich and diverse area that influences a multitude of fields including diagnostics, therapeutics, food, agriculture, personal care/cosmetics, and the environment.
2020 was an unusual year, for the first time, venture funding for microbiome companies substantially exceeded grant funding for microbiome research. In the year 2020, there were over 75K+ scientific publications, $1B+ grants awarded to microbiome research, ~150 ongoing clinical trials, and $1.5B+ venture funding. Does this mean that the microbiome market is evolving from being considered nascent to emerging/developing? To answer this question, let us dive deeper into the trends observed from the analytics of publications, grants, clinical trials, and venture funding.
Publication of scientific papers focused on microbiome research has been surging with over 75K publications in 2020 with stable growth of 24% in the past three years.
Catalyzed by landmark projects such as the Human microbiome project, the EU MetaHit projects, understanding of how the microbiome affects health and disease has exploded.
Majority is targeting GI diseases (gut dysbiosis, Inflammatory bowel disease), interactions between nutrition & gut microbiome and infectious diseases (C. difficile and antibiotic resistance )
Followed by research to understand the implication of the microbiome in immune diseases such as allergies, type 1 diabetes, thyroid, rheumatoid arthritis, and lupus
Numerous studies are investigating associations of microbiome and cancer, from oncogenesis and cancer progression to resistance or response to therapy
Several pioneering studies from 2006 including landmark projects such as the Human microbiome project, the EU MetaHit projects, laid the foundation for this field, showing an upward trend to 2019. For the first time, there was marked dip in funding amount in 2020. Funding dropped from ~$1.9B in 2019 to ~$1.1B in 2020, impacted by COVID. One could expect 2021 to catch up and reflect the 5 year upward trend from 2015- 2019 as several publicly traded life science companies such as Illumina have indicated that their core business can be expected to rebound in 2021.
Considerable grants are focused on basic biology studies characterizing microbial signaling in communities and functional studies within communities likely to catalyze our understanding of concepts such as quorum sensing and drive the field of microbiome engineering forward.
Environmental is garnering more attention with grants that are on tackling environmental pollution, climate change, and habitats.
The number of ongoing clinical trials with focus on the microbiome have risen substantially from 2015 –2019 to ~190 trials, with almost seven times the number of trials recorded in 2019 relative to 2015. Like in clinical trials in other spaces, COVID-19 has impacted the number of ongoing clinical trials in 2020. Thankfully, majority of these can be expected to re-initiate in 2021. 2020 also saw three key clinical trial successes that has spurred the industry, namely that of Seres, Rebiotix, and Finch. All three companies target recurrent C. diff infections, Seres announced that it has met its primary end point in a phase 3 trial, while Rebiotix/Ferring announce positive preliminary phase 3 data, and Finch release phase 2 data that showed statistically significant benefit. These breakthroughs are likely to pave the way for other indications. However, regulatory uncertainties regarding classification and frameworks for microbiome therapeutics continue to remain a barrier.
Key therapeutic approaches undertaken are:
Fecal Microbiota Transplantation (FMT): Introduces microbiota from a healthy donor by administering a preparation of fecal matter into a patient. The three clinical trials by Seres, Rebiotix, and Finch indicated above, are FMT candidate. Largely target infectious diseases and GI indications but limited by the need for donor stool, sample quality and safety concerns.
Live Biotherapeutic Product (LBP): This is the most favored mechanism which is introduction of hand-picked single strain or consortia of cultured microbes based on comparison of microbiome signature libraries of healthy and unhealthy individuals. Notable companies such as Seres, Vedanta, 4D, Evelo are targeting oncology, infectious disease, GI indications, metabolic, CNS, and immunology indications with this approach. Consistency, difficult to culture microbes, and complex formulation process are the key challenges.
Bacteriophage & Viruses: Introduction of bacteriophages to eliminate pathogenic bacteria or as a delivery vehicle for gene editing systems. Companies such as Eligo, Locus, BiomX, and Spero have all adopted this approach to target oncology, infectious disease, GI indications, and immunology. Generation of resistance, stability and gene transfer to other bacteria are concerns.
Small Molecules or Biologics: This is the newer way to modulate the microbiome by introducing biologically active molecules produced by the microbiome, rather than the microorganisms themselves. This approach to reprogram the microbiome with active molecules has been adopted by companies such as Kaleido, Enterome, Qualigen, and Second genome to target oncology, infectious disease, dermatology, metabolic, and neurology. However, questions remain on whether same level of coverage, durability of effect of LBPs can be seen.
Like other avenues in the healthcare space, investor enthusiasm has been the bright spot that has powered the market through the pandemic. Funding reached historic levels of ~$2B in 2020, US investors dominate, followed by EU, in France, UK, and Ireland.
Agriculture companies have galvanized the field by raising big amounts. A record breaking, nearly $700M was raised in 2020 by several breakout companies with transformational microbiome based soil management solutions such as IndigoAg, PivotBio, AgBiome. There is disruptive potential in this market, engineering of soil and a crop/plant’s microbiome can boost crop yield, improves plant health, ward off insects, sequester carbon and lower costs.
Diet has profound effects in shaping the composition of the gut microbiota. Increasing awareness of healthy diet to promote a healthy microbiome has led to proliferation of fiber, prebiotics, and probiotics. The food & beverage segment with nutrition and wellness solutions based on functional ingredients such as probiotics, prebiotics, and others to establish a healthy microbiome have received ample funding, e.g. Perfect Day, ByHeart.
Personalized nutrition that recommends individualized diet based on microbiome profile and chronic disease risk is incredibly attractive to consumers. Companies such as Viome, Day Two, and Vivante Health are vying to give consumers food recommendations based on microbiome testing, AI insights to support glycemic control, weight loss, ageing, restful sleep, and so on.
Therapeutics companies have consistently received funding buoyed by clinical trial successes in 2020. Besides GI, infectious disease, companies focused on areas such as oncology, CNS, metabolic and skin are receiving funding (Vedanta, Kallyope, Enterome, & Azitra). Companies like Enterome are employing omics platforms to generate precision drugs. Building a consistent drug product from the various therapeutic approaches requires time and investments. CDMO’s like Arranta Bio are garnering attention as well.
Hypothesis free infectious disease testing is the holy grail, Karius is making strides on this front and gained significant funding recently. Consumer companies are enabling microbiome profiling without clinical intervention to guide personalized nutrition and skincare.
Promise of environmental microbiome engineering to control harmful effects of pollution and climate change is electrifying to say the least. Growing levels of published research and grant funding indicates that the science is building and likely to be the next frontier of VC funding.
Consumers are increasingly looking to maintain beautiful looking skin with a healthy skin ecosystem , the industry is innovating with advanced ingredients, and new formulations. However, skin tends to be more challenging than the gut as the skin microbiome varies by skin site, hygiene level, and environmental conditions. This is where personalized cosmetics based on consumer microbiome profiling maybe the next frontier. However, since personal care products do not need to undertake rigorous studies, efficacy will always remain a question.
In conclusion, robust trends and ascent in venture funding implies transformational potential across multitude of industries. The microbiome market ecosystem is interconnected and mutually benefit from advances.
NOTE: Data for this article has been generated from Arogyam Microbiome Market Intelligence Report: https://www.arogyam.biz/product-page/single-user-license-analytics-of-the-microbiome-landscape