The human microbiome is an exciting revolutionary space which is captivating the interest of academia and industry alike. Consequently, the current human microbiome pipeline is emerging as a red- hot space with promising opportunities to develop innovative products.
The human microbiome pipeline can be divided into two major applications; therapeutics and diagnostic products. To date, no human microbiome therapeutic or diagnostic product has gained regulatory approval, leaving investors everything to play for. Pipeline therapeutics which modulate the human microbiome include fecal microbiota transplant (FMT), small molecules and live microbes. The human microbiome therapeutic pipeline encompasses a broad range of diseases including cancer, diabetes, asthma, atherosclerosis, nutrition, arthritis, neurological disorders and clostridium difficile infection (CDI). Currently, the human microbiome therapeutic pipeline involves a heated race-to-market for the treatment of CDI, featuring three late- stage products.
Rebiotix’s RBX2660 delivers live, human-derived microbes via enema into the Gl tract for treatment of recurrent CDI. Rebiotix recently announced it has begun its Phase III trial. Rebiotix’s Phase II trial, known as PUNCH CD found overall efficacy of RBX2660 at treating recurrent CDI was 87%. The Phase IIb PUNCH-CD 2 trial found efficacy was 88%; while the open-label Phase II trial, PUNCH Open Label, showed efficacy was 79% compared with a historical control of 52% (p<0.000). RBX2660 was found to be safe and well tolerated. RBX2660 has been granted FDA Fast Track, Orphan Drug and Breakthrough Therapy designations.
Seres Therapeutics/Nestlé Health Science’s SER-109 is a single-dose oral capsule consisting of bacterial spores enriched and purified from stool samples of healthy, screened human donors. In June 2017, SER-109 commenced its Phase III trial (ECOSPOR III) for the prevention of recurrent CDI. Phase /II results at eight weeks found 97% of patients achieved a clinical cure. Additionally, 87% of patients achieved no diarrhea associated with a positive test for C. difficile. ECOSPOR results at 24 weeks found relatively little new efficacy data compared to eight weeks. The Phase II open-label extension study ECOSPOR II found SER-109 led to a 32% recurrence rate. SER-109 was found to be safe and well tolerated. SER-109 has been granted FDA Orphan Drug and Breakthrough Therapy designations.
Synthetic Biologic’s SYN-004 (ribaxamase) is an oral tablet in Phase II development for the prevention CDI and antibiotic-associated diarrhea (ADD). SYN-004 is designed to degrade certain IV beta-lactam antibiotics within the GI tract and maintain the natural balance of the gut microbiome for the prevention of CDI, pathogenic overgrowth and the emergence of antimicrobial resistance (AMR). Phase IIb results found SYN-004 significantly reduced the risk of CDI by 71% versus placebo (p=0.045). Furthermore, SYN-004 significantly reduced new colonization by vancomycin-resistant enterococci versus placebo (p=0.0002). SYN-004 received Breakthrough Therapy Designation from the FDA for the prevention of CDI.
Other gastrointestinal Phase II pipeline candidates include Synthetic Biologics’ SYN-010 and Osel’s CBM588.
Synthetic Biologics’ SYN-010 is continuing to prepare for the initiation of pivotal Phase II/III clinical trials. SYN-010 is a modified-release formulation of lovastatin lactone designed to treat the underlying cause of irritable bowel syndrome with constipation (IBS-C).
Osel’s CBM588 is an oral Clostridium butyricum strain with a strong safety record undergoing development for antibiotic associated diarrhea and CDI. A Phase II study found CBM588 was safe. CBM588 has also been used safely in all age groups in Japan primarily for diarrheal disorders. Recent nonclinical studies support the use of CBM588 in treating IBS.
Other pipeline candidates to watch include:
- Osel’s Lactin-V live biotherapeutic product for recurrent UTI and Bacterial Vaginosis in Phase II development
- Microbiome Therapeutics’ NM504 for prediabetes and Type 2 diabetes; and NM505 for diabetes metformin gastrointestinal intolerance, both microbiome modulators in Phase I development
- Ritter Pharmaceutical’s RP-G28 an oral galacto-oligosaccharide microbiome modulator for lactose intolerance undergoing Phase IIb/III development
- Intrexon/Orgenics/Merck’s AG103 novel mouth rinse biotherapeutic for oral mucositis in Phase I development
The latest frontier of human microbiome research involves the development of diagnostic methods and tests that provide accurate assessment of the taxonomic compositions of microbiomes associated with complex samples.
Currently there is a head-to-head market race for two key colorectal cancer diagnostics; Metabiomic’s Colon Polyp and Colorectal Cancer Test and Origin Sciences’ Colorectal Cancer (CCR) Test. Metabiomics’ Colon Polyp and Colon Cancer Test is a non-invasive screening test for the detection of colon polyps and colorectal cancer. The Colon Polyp and Colon Cancer Test detects microbial biomarkers linked to dysbosis and colorectal cancer.
Origin Sciences’ CCR Test is under development for the detection of colorectal cancer in both asymptomatic and symptomatic patients. The CRC Test is designed to detect colorectal cancer using biomarker analysis of patient rectal mucosal samples collected using Origin Sciences’ proprietary OriCol device. A pilot study found that ELISA analysis of protein biomarkers collected with OriCol offers a pre-colonoscopy screening tool in patients referred under a two- week criteria rule. Data from the study suggests that a sensitivity of ≥95% can be achieved.
Although no human microbiome therapeutic or diagnostic product has gained FDA approval, promising new opportunities exist to develop novel therapeutics and diagnostic products across a wide range of diseases/therapeutic areas.
Join us to hear more on the human microbiome pipeline at Arrowhead’s 4th Annual Translational Microbiome Conference taking place in Boston, Massachusetts on April 18-20, 2018. (www.microbiomeconference.com)