Theriva Biologics, Inc. · AMEX:TOVX
Theriva Biologics — Synthetic Biologics — Rodman & Renshaw Global Investment Conference 2018
35 slides from Theriva Biologics's conference presentation, Sep 6, 2018
Slide 1: Rodman & Renshaw Global Investment Conference
September 6, 2018 Rodman & Renshaw Global Investment Conference Sponsored by H.C. Wainwright & Co. September 5, 2018 Steven A. Shallcross Interim CEO & CFO
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: About Synthetic Biologics
About Synthetic Biologics (NYSE American: SYN) • Diversified microbiome - focused company pioneering proprietary early & late - stage product candidates designed to protect and preserve the gut microbiome: • SYN - 004 (ribaxamase), for the prevention of antibiotic - mediated primary C. difficile inf
Slide 4: The Gut Microbiome: A Complex Community of Microbes
Containing bacteria, archaea, protists, fungi and viruses in the digestive tract The Gut Microbiome: A Complex Community of Microbes The microbiome affects our health • Immune system • Metabolism • Obesity • Inflammatory diseases • CNS disorders gut bacterial species have now been characterized >1,0
Slide 5: Building a Deep Pipeline Focused on the Microbiome
¹Degrades excess antibiotic excreted into the GI tract before the antibiotic reaches the colon and causes dysbiosis. ²Degrades non - absorbed antibiotic remaining in the GI tract before the antibiotic reaches the colon and causes dysbiosis. ³For use in patients who can’t swallow the capsule or its c
Slide 6: SYN-010
SYN - 010
Slide 7: Irritable Bowel Syndrome – Constipation (IBS-C)
Irritable Bowel Syndrome – Constipation (IBS - C) Up to 1 in 7 (14%) US adults has chronic constipation 2 $3,508 average additional healthcare cost per patient per year 3 Up to 1 in 20 (5%) US adults suffers from IBS - C 4 $3,856 average additional healthcare cost per patient per year 4 Only 8% of I
Slide 8: IBS and Constipation Markets are Growing
IBS and Constipation Markets are Growing More than 2x growth in 4 years! US IBS and Constipation Market 1 • Digital and DTC campaigns are enhancing awareness of both IBS and gut health • New entrants are growing the market , not cannibalizing it 1 • Only 26% of patients are “very satisfied” with cur
Slide 9: SYN-010 is a Unique Approach to Treating IBS-C
Directly targeting a microbial cause of IBS - C symptoms SYN - 010 is a Unique Approach to Treating IBS - C Bisacodyl Erythromycin Prucalopride Senna Linaclotide Lubiprostone Plecanatide Tenapanor Miralax Senna Target a Cause Hydrate the Stool Stimulate intestinal motility Stimulate intestinal water
Slide 10: How Does SYN-010 Work?
• Methane production (methanogenesis) is ubiquitous in the human intestine and is almost entirely due to the microorganism, M. smithii • Methane production in the human intestine caused by M. smithii has been shown to cause constipation, pain and bloating 1 • Modified - release formulation of lovast
Slide 11: SYN-010 Modified Release Lovastatin Lactone
Proactively targeting a cause of constipation, pain and bloating in IBS - C SYN - 010 Modified Release Lovastatin Lactone SYN - 010 ¹Hubert S et al. (2017) J Pharm Sci 107: 662 - 71 ²Morales W et al. (2015) Gastroenterology 148 (Suppl 1) :S - 779 - 80. Stomach pH 1.4 - 2.0 Duodenum pH 5.9 - 6.6 Jeju
Slide 12: SYN-010 Phase 2a Clinical Outcomes
18% 14% 0% 32% 45% 18% 5% 23% 21% 37% 11% 42% 56% 63% 39% 73% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% CSBM* PAIN OVERALL (FDA) BLOATING % Subjects with Indicated Response Placebo - Month 1 RCT SYN-010 21 mg - Month 1 RCT SYN-010 42 mg - Month 1 RCT SYN-010 42 mg - Months 2 & 3 EXT 52 51 51 51 22
Slide 13: Research Collaboration with Cedars-Sinai: Phase 2b Study
Co - funded, investigator - sponsored, Phase 2b clinical study of SYN - 010 Research Collaboration with Cedars - Sinai Clinic Visits Breath gases Cytokines in plasma Stool samples for microbiome - 14 1 14 28 42 56 70 84 DAY Randomize Screen Screening Pretreatmen t 12 - week Treatment Period EOS SYN
Slide 14: SYN-010 Patent Position
Pending Patent Applications • Formulations • Methods of Use in Specific Patient Populations • Clinical Dosing Expires 2035 Patented and Pending Methods of Treatment Treat Constipation with SYN - 010 in Screened Patients Expires 2034 Patented Methods of Treatment Broadest Indication Expires 2023 Exte
Slide 15: SYN-004 (ribaxamase)
SYN - 004 (ribaxamase)
Slide 16: A Healthy Microbiome Prevents Disease
A Healthy Microbiome Prevents Disease A healthy microbiome protects the body from infection Antibiotics disrupt the microbiome Pathogens Multiply opportunistic infections and resistance (AMR) New disease treatments intensified and AMR spreads Image Credit: CDC 7 Disruption of the microbiome enables
Slide 17: CDI: An Urgent Threat in the U.S. and Growing Global Concern
9. ., & McDonald, L.C; (2015). Emerging Infections Program C. difficile Surveillance Team. Burden of Clostridium difficile infection in the United States. New England Journal of Medicine. Retrieved from http://www.nejm.org/doi/full/10.1056/NEJMc1505190#t=article (Last accessed August 2017). 10. e, E
Slide 18: Antimicrobial Resistance (AMR)
• AMR is a serious global threat - world leaders are taking action • Leaders in industry and academia are developing action plans • Worldwide concern over potential “ Antibiotic Armageddon ” • ESCMID warns that Europe may surpass one - million deaths due to ineffective antibiotics by 2025 • Syntheti
Slide 19: What is ribaxamase?
• Two proprietary oral 75mg capsules (custom designed oral β - lactamase) • Designed to protect the natural balance of microbes in the gut microbiome during antibiotic use • Did not interfere with the efficacy of IV antibiotics in Phase 2 studies SYN - 004 (ribaxamase) • be co - administered with ce
Slide 20: SYN-004 (ribaxamase) to Prevent Dysbiosis
β - lactam antibiotic excreted into the GI tract can cause dysbiosis SYN - 004 (ribaxamase) to Prevent Dysbiosis Antibiotic Excreted in Bile ANTIBIOTIC EFFECTS Disrupted microbiome Proliferation of pathogens such as C. difficile Emergence of antimicrobial resistant species (AMR) Systemic (IV)
Slide 21: SYN-004 (ribaxamase) to Prevent Dysbiosis
Excreted β - Lactam Antibiotic Degrading excess β - lactam antibiotic excreted into the GI tract SYN - 004 (ribaxamase) to Prevent Dysbiosis SYN - 004 (ribaxamase) Antibiotic Excreted in Bile Systemic (IV) β - lactam antibiotic Treat Primary Infection (e.g. pneumonia) Stomach Duodenum Jejunum Ileum
Slide 22: SYN-004 (ribaxamase) Phase 2b Clinical Trial
• Patients admitted for treatment of LRTI at 54 sites (Europe, North America)¹ • Achieved primary endpoint • Reduced CDI incidence by 71.4% vs Placebo (1.0% vs 3.4% P=0.045)² • Suppressed AMR • Reduced VRE colonization by 43.9% vs Placebo (P=0.0002)² • Reduced expression of multiple AMR genes • Pres
Slide 23: SYN-004 (ribaxamase) Expansion Programs
• SYN - 004 (ribaxamase) considering potential opportunities in specialty populations where Phase 3 clinical trials may be smaller • SYN - 006 (oral carbapenemase) to prevent dysbiosis, CDI and AMR caused by excretion of IV carbapenem antibiotics into the intestine • Next - generation product for po
Slide 24: Worldwide Market Opportunity
Worldwide Market Opportunity All Antibiotics 77.3B Doses IV Penicillins and Cephalosporins 7.5B Doses Source: IMS Health 2017 – doses in standard units Carbapenems, Penicillins and Cephalosporins 49.6B Doses Our product pipeline covers 64 % of the World’s antibiotics and 57 % of the United States’ a
Slide 25: Planned Phase 3 Clinical Trial
• Anticipate one large, global, multi - center, randomized controlled clinical trial • Primary efficacy endpoint reduction of CDI incidence in SYN - 004 vs Placebo treatment group • Co - primary safety endpoint relative risk of mortality in SYN - 004 vs Placebo treatment groups • Up to 4,000 patient
Slide 26: Ribaxamase Patent Position
Pending Patent Applications • Methods of Manufacture • Clinical Dosing, Formulation • Methods of Treatment Expires 2035/6 Patented other β - Lactamase Composition of Matter & Uses Expires 2035 Patented ribaxamase Composition of Matter Expires 2031 Extensive patent portfolio, multiple protection stra
Slide 27: Preclinical Pipeline SYN-020
Preclinical Pipeline SYN - 020
Slide 28: Intestinal Alkaline Phosphatase (IAP)
Intestinal Alkaline Phosphatase (IAP) • IAP is an endogenous enzyme that is produced in the small intestine • IAP maintains GI homeostasis • Detoxifies inflammatory mediators • Endotoxin, bacterial DNA, flagellin, nucleotides • Tightens the gut barrier to mitigate “leaky gut” • Reduces systemic tran
Slide 29: IAP Manufacturing Breakthrough
• The clinical application of an oral IAP drug has been limited by manufacturing constraints • cIAP is extracted from calf intestines and costs up to $10,000/gm • Recombinant manufacturing platforms produce very low yields ( 10 - 500 mg/L ) • Developed stable cell lines that express 3 gm/L • SYN - 0
Slide 30: SYN-020 Path to Clinical Development
SYN - 020 Path to Clinical Development • Currently planning to pursue three lead indications • Enterocolitis associated with radiation therapy for cancer • Enterocolitis associated with checkpoint inhibitor therapy for cancer • Microscopic colitis • Based on a wealth of animal and human data, future
Slide 31: Investment Opportunity
Investment Opportunity
Slide 32: Strategic Priorities & Objectives
Strategic Priorities & Objectives • Announced key partnership with Cedars - Sinai Medical Center to advance SYN - 010 • Met with FDA in Q2 2018 to establish key components of Phase 3 clinical program for SYN - 004 • End of Phase 2 Meeting planned in Q3 2018 to solidify remaining elements of Phase 3
Slide 33: Milestones & Potential Value Drivers
Q3 Q4 Q1 Q2 Q3 Q4 Milestones & Potential Value Drivers * 2018 2019 SYN - 010 Agreement with Cedars - Sinai to conduct Phase 2b investigator - sponsored clinical study SYN - 010 Expected first patient dosed in Phase 2b investigator - sponsored clinical study SYN - 004 Expected results from EOP2 meeti
Slide 34: Investment Thesis
Investment Thesis • Diversified microbiome - focused company pioneering proprietary early & late - stage product candidates targeting large, unmet medical needs • A robust clinical development pipeline representing multiple potential pathways to market • SYN - 004 (ribaxamase), for the prevention of
Slide 35: Thank You
Thank You
Synthetic Biologics — Rodman & Renshaw Global Investment Conference 2018 on 6ix