Microbiome is a space with high potential, a fact underlined by the complete absence of microbiome-targeting treatments on the market. This therapeutic area is set to evolve significantly in the coming years as the current pipeline holds numerous potential candidates, with the majority still in the early stages of drug development and only four in late-stage trials for gastrointestinal (GI), dermatological and respiratory indications, says GlobalData.

GlobalData’s report, ‘Thematic Research: Microbiome-Targeted Therapeutics in Immunology’, reveals that 23 microbiome-targeting therapeutics are currently being developed in the US and the *5EU for GI, dermatological, and respiratory conditions. Each of these therapies aims to address these diseases by manipulating the microbiome.

Chris Pilis, Immunology Analyst at GlobalData, comments, “Most microbiome-targeting agents in the pipeline are in early stages of development: roughly half are in Phase I and half are in Phase II. Out of the 23 drugs, 13 are being investigated for GI indications, with the majority targeting ulcerative colitis (UC), whereas six and four are being developed for dermatological and respiratory conditions, respectively. Notably, many of the microbiome-targeting drugs for dermatological and respiratory indications are oral formulations, likely targeting these diseases via the gut-skin and gut-lung axes, respectively.”

The space is currently dominated by small- and mid-size biotech, however, Big Pharma players such as Takeda and Johnson & Johnson have shown increasing interest in this space lately with the development of the Phase II agent Sibofimloc (NCT03943446), and Phase I agent JNJ-72537634 (NCT03931447), respectively. Four therapies are in late-stage Phase II trials: 4D Pharma’s Blautix for irritable bowel syndrome (IBS), AOBiome’s B-244 for acne vulgaris and atopic dermatitis (AD), Evelo Biosciences’ EDP-1815 for psoriasis, and Seres Therapeutics’ SER-287 for UC. Of these agents, key opinion leaders interviewed by GlobalData were particularly enthusiastic about the prospects of 4D Pharma’s Blautix and AOBiome’s B-244, as both agents have already demonstrated promising data in Phase Ib or in early Phase II trials.

Pilis notes, “Decreased biodiversity and imbalance of bacterial levels in the gut microflora are involved in IBS manifestation, which is what Blautix is aiming to address. It is an oral formulation that releases single strains of commensal Blautia hydrogenotrophica that consume H2 gases causing bloating during the disease. The drug also induces acetate production, which promotes gut health, and increases microbiome diversity, ultimately trying to tackle both cause and effect of the disorder. Blautix is currently being evaluated in a Phase IIb trial (NCT03721107), but has exhibited encouraging efficacy and safety results in a previous Phase Ib trial.

“What is most promising about this candidate is that it is under investigation for both sub-groups of IBS-C and IBS-D patients, which until now have had very different therapeutic regimens. If successful, Blautix would be the first marketed product capable of treating both conditions. Consequently, this product could also be effective in treating IBS-M patients (one third of IBS cases) who to date have no treatments approved by the FDA or EMA. Ultimately, Blautix could have a strong impact on the market by being the first microbiome-targeting therapy for IBS and the first treatment approved for both IBS-C and IBS-D, which may potentially grant Blautix the exclusive market share of IBS-M patients.”

B-244 is a topical product under development by AOBiome for the treatment of acne and AD. GlobalData expects this product may gain popularity if marketed as a more ‘natural’ alternative to topical retinoids in acne and/or corticosteroids in AD. Thus far, B-244 has displayed good efficacy and tolerability for both acne and AD. It is currently in a Phase IIb trial (NCT04490109) for mild-to-moderate AD and has already been evaluated in a Phase IIb trial for mild-to-moderate acne (NCT02832063).

Pilis adds, “Although AOBiome read out positive data for NCT02832063 in 2017, the company has seemingly stalled development of B-244 in acne, possibly prioritising launch of the drug in AD. If successful in clinical trials, B-244 will be the first skin microbiome-targeting drug to enter the market. GlobalData believes its unique mechanism of action and potential to manage two distinct conditions may lead to strong uptake by patients.

“Products such as Blautix and B-244 in particular are microbiome-targeting candidates setting high expectations, by either meeting the unmet needs of difficult-to-treat patients or by addressing multiple indications.”

*5EU: France, Germany, Italy, Spain, UK