This document discusses live biotherapeutics (LBPs) which are live organisms used to prevent, treat, or cure diseases. It provides an overview of probiotics and next-generation probiotics (NGPs), the potential of LBPs to treat various diseases like gastrointestinal and dermatological conditions. The discovery and development process of LBPs including strain isolation, safety and efficacy evaluation, and mechanism research is described. Finally, the document outlines Creative Biolabs' services in LBP identification, testing, manufacturing and clinical development.

1. Live Biotherapeutics
Tel: 1-631-381-2994 Email: info@creative-biolabs.com
45-1 Ramsey Road, Shirley, NY 11967, USA
Developing next-generation probiotics to treat human diseases

2. What is Live Biotherapeutics？
The History of Probiotics and Next-generation Probiotics
The Potential of Biotherapeutics to Treat Disease
Live Biotherapeutics in Clinical Development
The Discovery and Development Process of Live Biotherapeutics
• Isolation, cultivation and identification of strains
• Safety evaluation of strains
• Drug efficacy Study
• Mechanism research
Creative Biolabs’ Live Biotherapeutics Services
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3. 1) contains live organisms, such as bacteria
2) is applicable to the prevention,
treatment, or cure of a disease or
condition of human beings
3) is not a vaccine
LBPs (live biotherapeutics)=NGPs (Next-generation probiotics) (Paul W. O‘Toole, et al., 2017)
What is Live Biotherapeutics？
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4. Th History of Probiotics and Next-generation Probiotics
1857-1864
Pasteur discovers
LAB as spoilage
organisms
1878
LAB isolated from
milk by Lister
1889
Bifidobacterium
described by
Tissier
1990
Bifidobacterium
described by
Moro
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5. 1907
Metchnikoff
describes Bulgarian
Bacillus associated
with health
1930
Shirota commercializes
fermented milk based
on Lactobacillus casei
isolate
1953
Kollath uses the term
probiotika for active
substances
promoting health
1965
Lilley and Stillwell define probiotics
as microbes that stimulate growth
of other microorganisms
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6. 1989
Fuller defines
probiotics as
beneficial microbial
supplements
2001
FAO/WHO
definition of
probiotics
2003
Genomic era: first
genome sequence of a
probiotic, Lactobacillus
plantarum
2005
Relman uses high-
throughput 16S amplicon
sequencing to catalogue
gut microbiome.
2016
FDA/CBER
guidelines for live
biotherapeutics
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7. Th Potential of Biotherapeutics to Treat Disease
21%
Dermatology
Eg. Psoriasis, acne,
atopic dermatitis
25%
Other
Eg. Cancer, CNS,
cardiovascular
13%
32%
8%
Endocrinology
Eg. Diabetes, obesity
Gastro-intestinal
Eg. Crohn's disease, IBD,
C. diff. infection
Genito-urinary
Eg. Infection, fertility issues
The potential of live biotherapeutics to treat disease
Therapeutic areas as % of total pipeline
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8. Name Organism Disease target Phase
Mutaflor Escherichia coli Nissle 1917 Irritable bowel syndrome (IBS) Approved
MIYAIRI 588 Clostridium butyricum Intestinal disorders Approved
RBX-2660 Lactobacillus rhamnosus GG Clostridium difficile infection Phase 3
IBP-9414 Lactobacillus reuteri Necrotizing enterocolitis Phase 3
AG013 Lactococcus lactis Oral mucositis and cancer Phase 2
VXM01 Salmonella typhi Ty21a Progressive glioblastoma Phase 2
LACTIN-V Lactobacillus crispatus CTV-05 Bacterial vaginosis Phase 2
SYNB1891 Escherichia coli Nissle 1917 Hyperammonemia Phase 2
APS001F Bifidobacterium longum Solid tumors Phase 1
ADXS-HOT Lysteria monocytogenes Non-small cell lung cancer Phase 1
Live Biotherapeutics in Clinical Development
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9.  Isolation, cultivation and identification of strains
 Safety evaluation of strains
 Drug efficacy Study
 Mechanism research
Graphical summary of the pathway to regulatory approval for live
biotherapeutic products.
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(Paul W. O‘Toole, et al., 2017)
The Discovery and Development
Process of Live Biotherapeutics
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10. Morphological characteristics of Bacteroidetes fragilis.
(Humin D, et al., 2016)
(a) Colony culture and colony morphology observation.
(b) Observations under an optical microscope after Gram-staining.
(c) Observations under a scanning electron microscope.
(d) Observations under a transmission electron microscope.
Isolation, cultivation and identification of strains
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11. Safety
evaluation
of
strains
Biological safety test of probiotic Streptococcus macedonicus strains. (Armin T, et al., 2020)
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12. Effects of A. muciniphila and derived products on host metabolism.
(Patrice D. Cani and Willem M. de Vos, 2017)
Akkermansia muciniphila treat the diseases
Drug efficacy study and mechanism research
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Drug efficacy study and mechanism research
Clostridium butyricum MIYAIRI 588 (CBM 588) treat the diseases
(Hagihara M, et al., 2020)
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14. Analytical Development and Qualification Services
for Live Biotherapeutic Products
Live Biotherapeutics Products cGMP Manufacturing
Creative Biolabs’ Live Biotherapeutics Services
 Microbial Identification
 Potency Test
 Gene Integration Stability Test
 Monocyte Activation Test
 Biological Safety Test
 Antibiotic Susceptibility/Resistance Test
 Determination of Bioburden
 In Vitro Tests of Immune System Modulation
 Host-Microbe Interaction Tests
……
Cell bank creating and preserving
Microbial fermentation, purification, stabilization, formulation,
all the way to packaging, fills, and lyophilization.
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15. Tel: 1-631-381-2994
info@creative-biolabs.com
45-1 Ramsey Road, Shirley, NY 11967, USA