LNC targets human trials this year as it steps up licencing and expands research

A new study helps to explain how nerve cells sense the microbes in the gut and how they coordinate their function with other tissues in the digestive tract.

French biotech LNC Therapeutics says it will launch the first ever in-human trials to dose with a single strain of Christensenella before the end of 2020, as the company looks to shift from a focus on pre-clinical and biodiscovery to become a clinical-stage biotech.

Speaking with Microbiome Post, Georges Rawadi, CEO of LNC Therapeutics said the company is looking to capitalize on its extensive IP and scientific foundation to become a leader in single-strain microbiome therapies.

“As a company we have evolved significantly in the past year, and we will continue doing so,” he said. “There is room to occupy in Europe in terms of the microbiome – and especially in terms of a single strain microbiome company. There are some leaders in the USA and in the UK, but I would say in mainland Europe is a place where LNC can continue building a leadership position – and that’s why we have been very aggressive in occupying that space and building out a pipeline of IP and products.”

After an early foray into the world of nutrition with its Stablor product, Rawadi says the company is now completely focused on a single strain therapeutics.

“We don’t do any more nutritional science or food application. That is where we started, and where we learned, and actually it built significant expertise, but now we are focusing on the therapeutic pipeline and on building on our IP, which is strongly based on the Christensenella family, and trying to expand and leverage that.”

Rawadi, who has worked with a number of biopharmaceutical firms including Celyad, Cellectis, Galapagos, ProStrakan and Sanofi-Aventis, says LNC has focused on building a large collection of single strain Christensenella. For each strain it has built an ID card containing key genetic and biochemical information.

“We believe we have the largest and most diverse private collection of Christensenella strains,” he said. “We have already spent quite a long time characterising them from genomic and biochemical standpoints.”

Clinical pipeline

In addition to developing its own library or strains, and building its own IP, the company has looked to agree multiple licencing deals with universities and other institutions that have expertise and patents in the area

In 2018 LNC signed an exclusive licence agreement with Cornell University for its family of patents and IP relating to Christensenella. The deal allowed LNC to further focus on candidate strains for conditions including obesity and metabolic disorders and resulted in the company’s first Christensenella-based drug candidate for the treatment of obesity – referred to as LNC-01.

Obesity is one of the first metabolic conditions that Christensenella has been suggested to play an important role. Indeed, studies have linked the presence of Christensenella with lean mass, while its absence has been associated with higher BMI, pre-diabetes, and an increase in many metabolic disease markers in human cohorts.

“Christensenella has been pointed out at the bacteria that is missing, basically in every single obese patient, and associated with a lot of metabolic disorders,” said Rawadi.

He noted that LNC has built ‘significant’ pre-clinical data showing its proof of concept for Christensenella in obesity, and that the company plans to move to a clinical-stages this year.

“Now we have very good understanding of what happens when you give this specific single strain of Christensenella to a mouse – and what the cascade of events are that occur to drive therapeutic activity,” he said. “The next step is to translate this into humans, and we are planning to start our first clinical trial in the USA before the end of 2020.”

New deal targets mood and anxiety

In recent weeks the Paris-based firm announced a further licencing deal with the Spanish National Research Council (CSIC) for its patent dedicated to the therapeutic applications of Christensenella gut bacteria in mood disorders.

The deal, which is based on the work of research teams led by Professor Yolanda Sanz at the Institute of Agrochemistry and Food Technology (IATA), gives LNC exclusive worldwide research, manufacturing and marketing rights of therapeutics developed for the treatment of mood disorders, such as depression or anxiety and becomes LNC’s fourth pipeline programme – known as LNC-02.

“There is exciting data for Christensenella relating to behaviour and mood of stressed animals,” said Rawadi. “There is data showing that when you stress animals, you can create behaviours and similar changes to those seen in depressed people or people who suffer with a high level of anxiety.”

“When you introduce Christensenella into these animals, you can reverse that behaviour, and this is really something that is exciting and innovative,” he commented, adding that it is already clear that the microbiome is associated with mood disorders through the gut-brain axis, and also limited data suggesting that people with mood disorders have reduced levels of Christensenella.

“With the licencing we have, there is the proof of concept that introducing certain strains of Christensenella have a significant impact on behaviour,” he said – noting that there is further exploratory work to be done in order to better understand mechanisms of actions and to understand the best ways to use the data to screen for other candidate strains within the LNC library.

Alongside the potential for treatment of clinical mood disorders, Rawadi suggested a big opportunity for benefit is in the prevention of full clinical diagnoses with a mood disorder in those who perhaps have mild symptoms such as sub-clinical anxiety and depression.

Attractive proposition

Rawadi says the fact that a single strain bacterial species us somewhat cheaper and easier to research and manufacture than many of the complex drugs that pharmaceutical companies are currently focusing on may provide benefits – both in terms of the ability to be used as preventative medicine, and also in terms of attracting investors.

“It’s not like an expensive medial therapy where it costs hundreds of thousands per year, and very few people with very severe conditions will be those who benefit,” he notes. “Here, there is an opportunity here to start doing preventional medicine with these kind of drugs.”

The CEO noted that the company is always looking for opportunities to connect with investors and at ways to raise money. The firm has already raised more than €22 million since its creation in 2010 –  with recent funding in 2017 drawing in €6.5 million from investors including Seventure Partners and a 2019 round for €6.2 million which included a capital increase for existing investors like Seventure, NACO (Nouvelle-Aquitaine region) and the European Union.

Rawadi said the company has the capital to at least complete the upcoming clinical trial in its LNC-01 candidate for obesity, but that the company continues to look for opportunities.

“We believe that we will be very attractive for investors and for pharma,” he said. “We are very confident in that we have a strong scientific rationale, the IP is there. We have gathered a great team. So, everything is there for us.

“Now we just need a little bit of luck in that all of the data that keeps coming in remains positive.”

Beyond Christensenella

Just as LNC starts to ramp up its clinical activities to further develop its pipeline of four drug candidates based on Christensenella, the company has also outlined ambitious plans to begin preliminary work beyond the Christensenella family.

“As we want to be a leader, we really want to capture all of the good opportunities and to start looking outside of Christensenella,” said Rawadi. “So we have been thinking about other bacteria that have similar applications to Christensenella, and have shown at least some efficacy.”

A recent partnership with INRA, the French National Institute of Agricultural Research, aims to explore other opportunities in inflammatory diseases, he said noting that LNC aims to remain focused on anti-inflammatory pathways related to chronic conditions, unlike some other companies that are taking approaches related to pro-inflammatory pathways.

“These pathways have different applications,” he noted. “People who are looking to combine for instance with cancer drugs are looking for pro-inflammatory bacteria that can actually stimulate the immune system and make it more active.”

“In our case, we work with bacteria that are anti-inflammatory, and we are building significant know-how in that space,” said the CEO. “Right now we focus on IBD, obesity and depression, and we want to remain in that space because we believe that treating for the long-term with something via the microbiome has sense.”

“Now we are exploring related indications, and other bacteria than Christensenella. This is still an exploratory project, but when we have all of the data we will be able to communicate more openly about that,” Rawadi told Microbiome Post.

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