Theriva Biologics, Inc. · AMEX:TOVX
Theriva Biologics — Synthetic Biologics — Investor Presentation (October 2018)
43 slides from Theriva Biologics's investor presentation, Oct 2, 2018
Slide 1: Corporate Presentation
1 October 2, 2018 Corporate Presentation
Slide 2: Forward-Looking Statements
2 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 statement
Slide 3: Our Leadership Team
3 Our Leadership Team Steven Shallcross, Interim CEO & CFO Vanda Pharmaceuticals, Inc., Empire Petroleum Partners, LLC, Innocoll AG (formerly privately held Innocoll Holdings, Inc.) Joseph Sliman, MD, MPH, CMO Vanda Pharmaceuticals, Inc., MedImmune , Inc., DynPort Vaccine Raymond Stapleton, PhD, SVP
Slide 4: About Synthetic Biologics
4 About Synthetic Biologics • 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 infection (CDI), patho
Slide 5: SYN Portfolio of Microbiome-Focused Therapies
5 AAD = antibiotic associated diarrhea; aGVHD = acute graft - vs - host disease (hematopoietic cell transplant patients); AMR = antimicrobial resistance; CDI = clostridium difficile infection; CIC = chronic idiopathic constipation; DR = delayed release; EOP2 = end - of - phase 2 meeting with the FDA
Slide 6: Milestones & Potential Value Drivers
6 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 (Cedars - Sinai) SYN - 004 Expected resu
Slide 7: SYN-004 (ribaxamase)
SYN - 004 (ribaxamase)
Slide 8: A Healthy Microbiome Prevents Disease
8 Healthy microbiome protects the body from disease Antibiotics disrupt the microbiome Pathogens multiply opportunistic infections and resistance (AMR) Image Credit: CDC A Healthy Microbiome Prevents Disease Disruption of the microbiome enables emergence and spread of pathogens New disease treatment
Slide 9: Preventing disruption of the microbiome can protect against pathogens
9 Healthy microbiome protects the body from disease Antibiotics disrupt the microbiome Image Credit: CDC A Healthy Microbiome Prevents Disease Preventing disruption of the microbiome can protect against pathogens and disease PREVENTION Synthetic Biologics Concept: Block the microbiome damaging agent
Slide 10: An Urgent Threat in the U.S. and Growing Global Concern
10 9. ., & McDonald, L.C; (2015). Emerging Infections Program C. difficile Surveillance Team. Burden of Clostridium difficile infec tion in the United States. New England Journal of Medicine. Retrieved from http://www.nejm.org/doi/full/10.1056/NEJMc1505190#t=a rticle (Last accessed August 2017). 10.
Slide 11: What is ribaxamase?
11 • 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
Slide 12: SYN-004 to Protect the Gut Microbiome
12 Degrading excess β - lactam antibiotic excreted into the GI tract SYN - 004 to Protect the Gut Microbiome Antibiotic Excreted in Bile Systemic (IV) β - lactam antibiotic Treat Primary Infection (e.g. pneumonia) Stomach Duodenum Jejunum Ileum Cecum Colon Excreted β - Lactam Antibiotic SYN - 004 (r
Slide 13: SYN-004 to Protect the Gut Microbiome
13 Degrading excess β - lactam antibiotic excreted into the GI tract SYN - 004 to Protect the Gut Microbiome SYN - 004 (ribaxamase) Antibiotic Excreted in Bile Systemic (IV) β - lactam antibiotic Treat Primary Infection (e.g. pneumonia) Stomach Duodenum Jejunum Ileum Cecum Colon Enteric protection i
Slide 14: SYN-004 Phase 2b Clinical Trial
14 • Patients admitted for treatment of pneumonia (LRTI) at 54 sites (Europe, North America)¹ • Achieved primary endpoint • Reduced C. diff infection (CDI) incidence by 71.4% vs Placebo (1.0% vs 3.4% P=0.045)² • Suppressed antimicrobial resistance (AMR) • Reduced vancomycin - resistant enterococci (
Slide 15: Worldwide Market Opportunity
15 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
Slide 16: SYN-004 Development Status
16 • Anticipate 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 group • Evaluate a broad rang
Slide 17: Prevention of aGVHD in Allogeneic HCT Recipients
17 • Prevention of acute graft - versus - host disease (aGVHD) in Allogeneic Hematopoietic Cell Transplantation (HCT) recipients • An estimated 8,539 allogeneic HCT procedures were conducted in the USA in 2016 1 • ~4,500 procedures conducted in China 2 • 80 - 90% of allogeneic HCT recipients will be
Slide 18: SYN-004 Patent Position
18 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 SYN - 004 (ribaxamase) Composition of Matter Expires 2031 Extensive patent portfolio, multiple
Slide 19: SYN-010
SYN - 010
Slide 20: Irritable Bowel Syndrome – Constipation (IBS-C)
20 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% o
Slide 21: IBS and Constipation Markets are Growing
21 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
Slide 22: SYN-010 is a Unique Approach to Treating IBS-C
22 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 wa
Slide 23: How Does SYN-010 Work?
23 • 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 lov
Slide 24: SYN-010 Modified Release Lovastatin Lactone
24 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 J
Slide 25: SYN-010 Phase 2a Clinical Outcomes
25 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
Slide 26: Phase 2b Study with Cedars-Sinai
26 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 S
Slide 27: SYN-010 Patent Position
27 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 E
Slide 28: SYN-020
SYN - 020
Slide 29: Intestinal Alkaline Phosphatase (IAP)
29 Intestinal Alkaline Phosphatase (IAP) • IAP is an endogenous enzyme that is produced in the small intestine • IAP maintains GI homeostasis 1,2 • Detoxifies inflammatory mediators 3 • Tightens the gut barrier to mitigate “leaky gut” 4 • Reduces systemic translocation of endotoxin and bacteria 5 •
Slide 30: SYN-020 Potential Indication: Radiation Therapy
30 • Radiation is used in 50% of cancer patients and has a role in 25% of cures 1 • Pelvic and abdominal irradiation is used >300,000 times annually in US • 60 - 80% of radiation - treated patients suffer acute bowel toxicity 1 • Estimated that 20 - 50% of survivors progress to chronic enteropathy •
Slide 31: Investment Opportunity
Investment Opportunity
Slide 32: Strategic Priorities
32 Strategic Priorities • Announced key partnership with Cedars - Sinai Medical Center to advance SYN - 010 • End of Phase 2 Meeting with FDA in Q3 2018 to solidify Phase 3 clinical program for SYN - 004 • Establish cost - effective development pathway for expansion indication for SYN - 004 in speci
Slide 33: Financial Snapshot: Capitalization Table
33 Financial Snapshot Synthetic Biologics, Inc. Capitalization Table October 1, 2018 Common Shares Outstanding 7,208,320 Stock Options Issued (2007 & 2010 Plans) 1 347,765 (4.8%) Total Outstanding Warrants 2 915,852 (12.7%) Common Shares for Future Grants 670,674 (9.3%) Series A Preferred Shares 3 6
Slide 34: Appendix
APPENDIX
Slide 35: SYN-004 (ribaxamase) Expansion Programs
SYN - 004 (ribaxamase) Expansion Programs
Slide 36: SYN-004 (ribaxamase) Franchise Programs
36 • SYN - 007: new oral formulation of ribaxamase for co - administration with oral β - lactam antibiotics • Novel formulation did not alter systemic PK of oral amoxicillin in pigs¹ and dogs • Preserved intestinal microbiome and suppressed AMR genes in pigs and dogs • SYN - 006: oral carbapenemase
Slide 37: SYN-004 Competitive Differentiation: CDI Landscape
37 Dysbiosis Current landscape for CDI prevention and treatment SYN - 004 (ribaxamase) Competitive Differentiation Infection (e.g. LRTI) Antibiotic Treatment & Management Recurrence Transmission C. difficile colonization bloom and toxigenesis ¹Cochrane Database of probiotic - treated patients did no
Slide 38: SYN-004 Competitive Differentiation
38 Dysbiosis Unique preventative agent reduces need for other products SYN - 004 (ribaxamase) Competitive Differentiation Infection (e.g. LRTI) Antibiotic Treatment & Management Recurrence Transmission ¹Cochrane Database of probiotic - treated patients did not show a reduction in CDI based on detect
Slide 39: SYN-004 Development: Cost-Benefit Analysis
39 SYN - 004 Development: Cost - Benefit Analysis Broad Indication Estimated Clinical Trial Size (n) Estimated Value Current proposed Phase 3 Endpoint: CDI reduction Incidence rate: 3 - 4% USD $80 - 100M Phase 3 Partnership/Funding Dependent Narrow Indication 3,000 - 4,000 800 - 1,000 200 - 500 Expa
Slide 40: Allogeneic Hematopoietic Cell Transplantation (HCT)
40 • Patients with a hematologic disorder have their diseased cells removed or destroyed and replaced by healthy hematopoietic stem cells ( HSCs ) from a related or unrelated donor • Donor HSCs may be derived from bone marrow, peripheral blood or umbilical cord blood • HLA matching is required to mi
Slide 41: Allogeneic HCT and Critical Adverse Outcomes
41 Allogeneic HCT and Critical Adverse Outcomes ¹ aGVHD first - line (steroid) therapy fails in ≥50% patients and overall 2 - year survival for patients with steroid refractory aGVHD is a s low as 20% ² VRE bacteremia has extremely high mortality (88%) in allogeneic HCT recipients; Enterococcal domi
Slide 42: Clinical Trial Concepts for aGVHD Prevention
42 • Rationale for Primary Endpoint • Decreased microbiome diversity due to IV β - lactam antibiotics is strongly associated with aGVHD ¹ ‒ aGVHD occurs in 40 - 60% of allogeneic HCT recipients • Prevention of aGVHD in allogeneic HCT recipients is critical to patient outcomes and survival² ‒ First -
Slide 43: Clinical Considerations in Allogeneic HCT
43 Clinical Considerations in Allogeneic HCT Parameter Details Initial Queries, Comments Patient Hematological malignancies (e.g. ALL, AML) Myeloproliferative neoplasms (e.g. CML) Only adults? Exclude non - malignant (aplastic anemia, thalassemia)? Donor type Matched related donor ( MRD ); unrelated
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