Probiota 2019

No guts, no glory: ‘Microbiome science ready to enter pharma arena,’ CEO of LNC Therapeutics says

By Will Chu

- Last updated on GMT

Georges Rawadi (4th from left) takes part in a panel discussion at this year's Probiota.
Georges Rawadi (4th from left) takes part in a panel discussion at this year's Probiota.
Microbiome science is mature enough to enter the pharma field, according to the CEO of a microbiota-focused drug developer, who presented at Probiota Copenhagen earlier this month.

Georges Rawadi’s comments come as nutrition and pharma form an ever-closer relationship that both place the gut microbiome at the centre of research and development efforts.

Speaking to NutraIngredients on the prospect of entering the pharmaceutical arena with his firm’s Christensenella​-based drug candidate, the head of LNC Therapeutics said, “There is no other pharmaceutical product on the market that has a similar mode of action.

“It is true that we are navigating within unclear regulatory waters but this is a situation that is similar to cell therapies 10 years ago,”​ he added.

“We are confident that we can bring live biotherapeutic (LBP) products into clinic relatively quickly and will be able to demonstrate efficacy.”

The Bordeaux-based firm are currently in the midst developing a drug candidate that targets the gut microbiota and its role in energy metabolism and the onset of obesity and metabolic disorders.

Christensenella characterised

Key to this is Christensenella​, a ba​cterial strain found in the gut that plays a role in fat reduction, lean mass, and lowering of obesity.

In his presentation at the event, Rawadi refers to a large body of research that presents a convincing argument to the strain’s relationship with body weight.

Amongst the selection, US researchers found that gut species richness was reduced​ and overall composition altered in obese (but not overweight) compared to healthy-weight participants.

Obesity was characterised by increased abundance of class Bacilli​ and its families Streptococcaceae ​and Lactobacillaceae​, and decreased abundance of several groups within class Clostridia​, including Christensenellaceae, Clostridiaceae​, and Dehalobacteriaceae.

Georges Rawadi 3
Dr Georges Rawadi, CEO of LNC Therapeutics. ©GeorgesRawadi

A similar study​ found Christensenellaceae​ and associated strains in the gut were enriched in individuals with low body mass index (BMI).

“There are only a handful of molecules that are approved as anti-obesity treatments and all are associated with severe side effects,”​ explained Rawadi. “Consequently, their use is extremely limited, to the point that only 1.3% of eligible obese Americans are currently treated.

“Christensenella-based therapy is different because we expect a very low toxicity. The mechanism of action of our Christensenella-based therapy is fundamentally different from existing molecules because it is the only one to act on the gut microbiota-host energy metabolism interface.

“As such, it is able to restore the functions of a healthy microbiome, improving nutrient and energy metabolism.”

Microbiome-based activity

The interest in microbiome-based therapeutics is gaining momentum with the prospect of interventions that promote a healthy microbiome as key to curbing chronic conditions such Crohn’s disease, autism, obesity and diabetes.

Other health conditions such as acne, psoriasis, allergies and gastrointestinal ailments were focus of an agreement​ between UK-based Microbiotica and Roche-owned biotechnology group Genentech as they pooled resources in the hunt for new microbiome-based therapeutics and biomarkers for its inflammatory bowel disease (IBD) pipeline.

Inked in June last year, the deal looks to harness artificial intelligence (AI) to hunt for biomarker signatures of drug response, new live bacterial therapeutics and novel targets for IBD.

The deal is Genentech’s second in the microbiome space in the past month, after the firm previously paired up with Lodo Therapeutics to search for new medicines based on microbial DNA found in soil.

“It is now established that the gut microbiota significantly contribute to energy metabolism and to the development of obesity-related disorders,”​ said Rawadi.

“This effect is mediated by a direct impact on nutrient intake and an indirect influence of the immune system, which we know is tightly associated with the development of severe conditions such as type 2 diabetes, NAFLD / NASH and even some cancers.

Rawadi went on to explain that in addition to this gut microbes influence behaviour and could also be targeted to modulate dietary behaviours.

“Humans, and generally all animals, have co-evolved along microbes, which explains such an intricate relationship,” ​he said.

“Therefore, we believe that understanding this complex interplay is key to address the root cause of metabolic disorders.”

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