Entering First-in-Human Clinical Study With a Single-Strain Live Biotherapeutic Product: Input and Feedback Gained From the EMA and the FDA

Paquet, Jeanne-Céleste; Claus, Sandrine P.; Cordaillat-Simmons, Magali; Mazier, Wilfrid; Rawadi, Georges; Rinaldi, Laure; Elustondo, Frédéric; Rouanet, Alice

doi:10.3389/fmed.2021.716266

Cited by 21 publications

(18 citation statements)

References 16 publications

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“…Finally, the selected C. minuta clinical candidate, strain DSM 33715 ( C. min 22), was characterized following current regulatory guidelines appropriate for further drug development 38 . The characterization panel revealed high similarity with previously described C. minuta strains 5 , 18 but DSM 33715 ( C. min 22) slightly differed from the others at the biochemical level (negative for salicin and positive for mannose metabolism) but these modest differences are not sufficient to explain differences in anti-inflammatory effects.…”

Section: Discussionmentioning

confidence: 99%

Selection of a novel strain of Christensenella minuta as a future biotherapy for Crohn’s disease

Relizani¹,

Corf²,

Kropp

et al. 2022

Sci Rep

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Microbiome-based therapies for inflammatory bowel diseases offer a novel and promising therapeutic approach. The human commensal bacteria of the species Christensenella minuta (C. minuta) have been reported consistently missing in patients affected by Crohn’s disease (CD) and have been documented to induce anti-inflammatory effects in human epithelial cells, supporting their potential as a novel biotherapy. This work aimed at selecting the most promising strain of C. minuta for future development as a clinical candidate for CD therapy. Here, we describe a complete screening process combining in vitro and in vivo assays to conduct a rational selection of a live strain of C. minuta with strong immunomodulatory properties. Starting from a collection of 32 strains, a panel of in vitro screening assays was used to narrow it down to five preclinical candidates that were further screened in vivo in an acute TNBS-induced rat colitis model. The most promising candidate was validated in vivo in two mouse models of colitis. The validated clinical candidate strain, C. minuta DSM 33715, was then fully characterized. Hence, applying a rationally designed screening algorithm, a novel strain of C. minuta was successfully identified as the most promising clinical candidate for CD.

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Section: Discussionmentioning

confidence: 99%

Selection of a novel strain of Christensenella minuta as a future biotherapy for Crohn’s disease

Relizani¹,

Corf²,

Kropp

et al. 2022

Sci Rep

Self Cite

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“…Besides the nutritional strategies, Blautia faecis DSM33383 could be developed as a therapeutic drug, either through its supernatant, isolated bioactive compounds, or as a Live Biotherapeutic Product [ 53 ]. To reach this pharmaceutical status, the requirements are also based on further characterization, safety concerns, and more preclinical and clinical evidence [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

Description of a Newly Isolated Blautia faecis Strain and Its Benefit in Mouse Models of Post-Influenza Secondary Enteric and Pulmonary Infections

et al. 2022

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The expanding knowledge on the systemic influence of the human microbiome suggests that fecal samples are underexploited sources of new beneficial strains for extra-intestinal health. We have recently shown that acetate, a main circulating microbiota-derived molecule, reduces the deleterious effects of pulmonary Streptococcus pneumoniae and enteric Salmonella enterica serovar Typhimurium bacterial post-influenza superinfections. Considering the beneficial and broad effects of acetate, we intended to isolate a commensal strain, producing acetate and potentially exploitable in the context of respiratory infections. We designed successive steps to select intestinal commensals that are extremely oxygen-sensitive, cultivable after a freezing process, without a proinflammatory effect on IL-8 induction, and producing acetate. We have identified the Blautia faecis DSM33383 strain, which decreased the TNFα-induced production of IL-8 by the intestinal epithelial cell line HT-29. The beneficial effect of this bacterial strain was further studied in two preclinical models of post-influenza Streptococcus pneumoniae (S.p) and Salmonella enterica serovar Typhimurium (S.t) superinfection. The intragastrical administration of Blautia faecis DSM33383 led to protection in influenza-infected mice suffering from an S.p. and, to a lesser extent, from an S.t secondary infection. Altogether, this study showed that Blautia faecis DSM33383 could be a promising candidate for preventive management of respiratory infectious diseases.

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“…The approval of these innovative products is promising but also constitute a challenge due to the limited experience of both applicants and regulators in defining quality and safety criteria and developing suitable study designs to demonstrate efficacy. Despite this, collaboration between the Pharmabiotic Research Institute (PRI) and industrial partners and scientists provides a roadmap ( Paquet et al, 2021 ).…”

Section: Example Success Storiesmentioning

confidence: 99%

Microbiome Research as an Effective Driver of Success Stories in Agrifood Systems – A Selection of Case Studies

et al. 2022

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Increasing knowledge of the microbiome has led to significant advancements in the agrifood system. Case studies based on microbiome applications have been reported worldwide and, in this review, we have selected 14 success stories that showcase the importance of microbiome research in advancing the agrifood system. The selected case studies describe products, methodologies, applications, tools, and processes that created an economic and societal impact. Additionally, they cover a broad range of fields within the agrifood chain: the management of diseases and putative pathogens; the use of microorganism as soil fertilizers and plant strengtheners; the investigation of the microbial dynamics occurring during food fermentation; the presence of microorganisms and/or genes associated with hazards for animal and human health (e.g., mycotoxins, spoilage agents, or pathogens) in feeds, foods, and their processing environments; applications to improve HACCP systems; and the identification of novel probiotics and prebiotics to improve the animal gut microbiome or to prevent chronic non-communicable diseases in humans (e.g., obesity complications). The microbiomes of soil, plants, and animals are pivotal for ensuring human and environmental health and this review highlights the impact that microbiome applications have with this regard.

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Entering First-in-Human Clinical Study With a Single-Strain Live Biotherapeutic Product: Input and Feedback Gained From the EMA and the FDA

Cited by 21 publications

References 16 publications

Selection of a novel strain of Christensenella minuta as a future biotherapy for Crohn’s disease

Selection of a novel strain of Christensenella minuta as a future biotherapy for Crohn’s disease

Description of a Newly Isolated Blautia faecis Strain and Its Benefit in Mouse Models of Post-Influenza Secondary Enteric and Pulmonary Infections

Microbiome Research as an Effective Driver of Success Stories in Agrifood Systems – A Selection of Case Studies

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