Theriva Biologics, Inc. · AMEX:TOVX
Theriva Biologics — Synthetic Biologics — Technical Presentation (May 2017)
23 slides from Theriva Biologics's technical presentation, May 4, 2017
Slide 1: Phase 2b Clinical Trial Results SYN-004 (ribaxamase)
Phase 2b Clinical Trial Results SYN - 004 (ribaxamase) May 4, 2017 www.syntheticbiologics.com
Slide 2: Forward-Looking Statements
Forward - Looking Statements This presentation includes forward - looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 , as amended, on Synthetic Biologics’ current expectations and projections about future events . In some cases forward - looking statements
Slide 3: SYN-004 (ribaxamase)
SYN - 004 (ribaxamase) Designed to prevent primary C. difficile Infection (CDI), pathogenic overgrowth and the emergence of antimicrobial resistance (AMR) in the gut microbiome
Slide 4: Antibiotic Effects on the Gut Microbiome
• Antibiotics disrupt the balance of commensal microbial species and enable the overgrowth of opportunistic pathogens. • Disruption of the natural balance of the microbiome (termed dysbiosis ) is multifactorial, but antibiotics have the most profound effect • Antibiotic - mediated alterations to the
Slide 5: Antibiotics Cause Intestinal Dysbiosis
Antibiotic is excreted into the GI tract after IV dosing Antibiotics Cause Intestinal Dysbiosis 5 Bile Disrupted microbiome Proliferation of pathogens such as C. difficile Enables emergence of resistant species Systemic Antibiotic Treat Infection Stomach Duodenum Jejunum Ileum Cecum Colon Exce
Slide 6: Prevents Intestinal Dysbiosis
Degrades antibiotic excreted into the GI tract SYN - 004 (ribaxamase) Prevents Intestinal Dysbiosis 6 No Drug Release SYN - 004 Bile Systemic Antibiotic Treat Infection Stomach Duodenum Jejunum Ileum Cecum Colon Antibiotic Degraded x Healthy, diverse microbiome x Suppresses prolifera
Slide 7: Protection of the Microbiome
Measuring eradication, overgrowth, diversity and recovery SYN - 004 (ribaxamase) Protection of the Microbiome 7 ¹Ceftriaxone in - patient IV dosing regimen and length of dosing were determined by local standard - of - care ²16S sequencing conducted by DNA Genotek Treatment Period 1 Follow - up 2 Scr
Slide 8: Phase 2b Topline Results
Data consistent with MoA of protecting gut microbiome from complications of antibiotic therapy SYN - 004 (ribaxamase): Phase 2b Topline Results 0 1 2 3 4 5 6 7 8 9 Local Lab Central Lab Patients Treated for CDI Placebo Ribaxamase P=0.045 P=0.027 P=0.007 *New colonization was defined as a negative sc
Slide 9: Protected Microbial Diversity (alpha-diversity)
Prevented CRO - mediated loss of α - diversity and enhanced microbiome recovery SYN - 004 (ribaxamase) Protected Microbial Diversity 9 ¹Shannon Index and Chao1 represent α - diversity, a measure of the microbial community composition within a sample ²Size of each ball is relative to the standard err
Slide 10: Protected Microbial Diversity (beta-diversity)
Prevented CRO - mediated loss of β - diversity and enhanced microbiome recovery SYN - 004 (ribaxamase) Protected Microbial Diversity 10 Placebo Ribaxamase Principle coordinate analysis of the β - diversity (unweighted Unifrac ) of patient samples. β - diversity is the community composition of two di
Slide 11: Protected Microbial Diversity: Screening Samples
Prevented CRO - mediated loss of β - diversity and enhanced microbiome recovery SYN - 004 (ribaxamase) Protected Microbial Diversity 11 Placebo Ribaxamase T0 T0 Screening samples are similar with regards to β - diversity in both groups Data are principle coordinate analysis of the β - diversity (unw
Slide 12: Protected Microbial Diversity: T1 Loss in Placebo
Prevented CRO - mediated loss of β - diversity and enhanced microbiome recovery SYN - 004 (ribaxamase) Protected Microbial Diversity 12 Placebo Ribaxamase T0 T0 T1 T1 Placebo samples display a significant loss of β - diversity as compared with ribaxamase at T1 Data are principle coordinate analysis
Slide 13: Protected Microbial Diversity: Recovery by T2
Prevented CRO - mediated loss of β - diversity and enhanced microbiome recovery SYN - 004 (ribaxamase) Protected Microbial Diversity 13 Placebo Ribaxamase T0 T0 T1 T1 T2 T2 By T2 the ribaxamase samples have recovered to their starting diversity but the placebo samples still display a significant los
Slide 14: Heat Map Comparison of Gut Microbes at T0 & T1
Heat Map Comparison of Gut Microbes at T0 & T1 Ribaxamase protects the gut microbiome from antibiotic - induced changes Placebo Ribaxamase T0 T1 T0 T1 ¹Data are a representative subset of all patients in each treatment group ²Each square represents the proportion of a particular species of microflor
Slide 15: Heat Map Comparison of Gut Microbes at T0 & T1
Heat Map Comparison of Gut Microbes at T0 & T1 Ribaxamase protects the gut microbiome from antibiotic - induced changes Placebo Ribaxamase T0 T1 Loss of Gut Microbes Overgrowth of Gut Microbes T0 T1 ¹Data are a representative subset of all patients in each treatment group ²Each square represents the
Slide 16: Heat Map Comparison of Gut Microbes at T0 & T1
Heat Map Comparison of Gut Microbes at T0 & T1 Ribaxamase protects the gut microbiome from antibiotic - induced changes Placebo Ribaxamase T0 T1 Loss of Gut Microbes Overgrowth of Gut Microbes T0 T1 Prevents Loss of Gut Microbes Prevents Overgrowth Of Gut Microbes ¹Data are a representative subset o
Slide 17: Phase 2b Summary of Results
• SYN - 004 achieved primary endpoint from Phase 2b, demonstrating a statistically significant relative risk reduction of 71.4% (p=0.045) in CDI rates versus placebo • Significant reduction in new colonization by vancomycin - resistant enterococci (VRE) for patients receiving ribaxamase versus place
Slide 18: Next Steps
• Analysis of additional exploratory endpoints to evaluate ability of ribaxamase to prevent proliferation of AMR in gut microbiome • Contract awarded by CDC BAA for microbiome assessment and intervention to address antibiotic - mediated AMR • Expect to meet with CDC following completion of analysis
Slide 19: Appendix
Appendix
Slide 20: Prevented Ceftriaxone-Mediated Loss of Alpha-Diversity
Prevented ceftriaxone - mediated loss of α - diversity and enhanced microbiome recovery SYN - 004 (ribaxamase) Protected Microbial Diversity 20 Alpha diversity is a measure of the community composition within an individual sample α - diversity • Observed OTUs • Chao1 Diversity • Shannon Diversity
Slide 21: Antibiotic-associated Diarrhea: Phase 2b Results
Antibiotic - associated Diarrhea SYN - 004 (ribaxamase): Phase 2b Results 21 0 5 10 15 20 25 30 All Cause Diarrhea Non-CDI AAD As per stool log Treated for diarrhea Placebo Ribaxamase P=0.113 P=0.059 P=0.043 • P - values are 1 - sided based on the pre - specified Z - test
Slide 22: New C. difficile Colonization: Phase 2b Results
New C. difficile c olonization at 72 hrs & 4 weeks 22 SYN - 004 (ribaxamase): Phase 2b Results 0 2 4 6 8 10 12 14 16 18 20 72 hours 4 weeks Placebo Ribaxamase • New colonization is negative on screening and then positive on a subsequent sample • P - values are 1 - sided based on the pre - specified
Slide 23: Phase 2b Clinical Trial Results
Phase 2b Clinical Trial Results SYN - 004 (ribaxamase) May 4, 2017 www.syntheticbiologics.com
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