Theriva Biologics, Inc. · AMEX:TOVX
Theriva Biologics — Synthetic Biologics — Investor Presentation (June 2016)
39 slides from Theriva Biologics's investor presentation, Jun 27, 2016
Slide 1: Investor Slide Deck June 2016
Investor Slide Deck June 2016
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: Company Highlights
Company Highlights • Advancing and developing gut microbiome therapeutics while targeting pathogen - specific diseases • Two lead microbiome - focused, billion - dollar market potential drug candidates in Phase 2 • SYN - 010 is the only therapeutic in development that targets etiology of IBS - C sym
Slide 4: Management Team
Management Team • Jeffrey Riley, CEO Pfizer, Nichols Institute (Quest), SmithKline Beecham, QIC • Steven Shallcross , CFO Vanda Pharmaceuticals, Inc., Empire Petroleum Partners, LLC, Innocoll AG (formerly privately held Innocoll Holdings, Inc.) • Joseph Sliman, MD, MPH, SVP Clinical/Regulatory Vanda
Slide 5: Product Pipeline
Product Pipeline 5 C - Cedars - Sinai Medical Center collaboration I - Intrexon Corporation collaboration T - The University of Texas at Austin collaboration Completed Planned Therapeutic Area / Product Candidate Discovery Preclinical Phase 1 Phase 2 Phase 3 IBS - C SYN - 010 C Oral modified - relea
Slide 6: Milestones: Achieved & Upcoming
Milestones: Achieved & Upcoming Therapeutic Area/Product Candidate Timeline IBS - C – SYN - 010: Phase 2 (1 st study; acute, placebo - controlled) 2Q 2015 – Initiated Phase 2 4Q 2015 – Reported Phase 2 topline data Phase 2 (2 nd study; extension, SYN - 010 42mg) 4Q 2015 – Initiated Phase 2 1Q 2016 –
Slide 7: Human Microbiome
Source: http://commonfund.nih.gov/hmp/overview.aspx US National Library of Medicine. Image source: Ottman N, et al. (2012) The function of our microbiota: who is out there and what do they do? Front. Cell. Inf. Microbio . 2:104. Human Microbiome > 1,000,000 Genes Human Genome 23,000 Genes 99% of Gen
Slide 8: Diseases Directly Influenced by the Gut Microbiome
Source: Belizário JE and Napolitano M (2015) Human microbiomes and their roles in dysbiosis , common diseases, and novel therapeutic approaches. Front. Microbiol . 6:1050. Diseases Directly Influenced by the Gut Microbiome 8 Microbial communities provide ample therapeutic targets Obesity Metabolic S
Slide 9: SYN-010: Treatment of IBS-C
SYN-010 Treatment of IBS-C = Dos
Slide 10: SYN-010: Proprietary Modified-Release Lovastatin Lactone
SYN - 010: Proprietary Modified - Release Lovastatin Lactone Designed to reduce methane production by M. smithii in the intestine Bacteroides thetaiotaomicron is one such bacterium Carbohydrates Methanobrevibacter smithii archea consumes hydrogen gas from Bacteroides and produces methane, which is l
Slide 11: SYN-010 Inhibits Methane Formation
Source: Gottlieb, K., et al . "Review article: inhibition of methanogenic archaea by statins as a targeted management strategy for constipation and related disorders." Alimentary Pharmacology & Therapeutics 43.2 (2016): 197 - 212. SYN - 010 Inhibits Methane Formation 11 Anti - methanogenic therapy t
Slide 12: IBS-C Market Overview
12 IBS - C Market Overview 1 SYN - 010 targets an underlying cause vs competition Product Candidate SYN - 010 * Linzess Amitiza OTC Laxatives Plecanatide Tenapanor Company Synthetic Allergan Takeda Various Synergy Ardelyx Phase/Status Phase 2 Marketed Marketed Marketed Phase 3 Phase 3 Treat underlyi
Slide 13: SYN-010 Evaluated in IBS-C Patients in 2 Contiguous Studies
13 Subjects who successfully completed Study 1 were transferred to active drug at Day 29 SYN - 010 Evaluated in IBS - C Patients in 2 Contiguous Studies 1 SYN - 010 21 mg (22) Placebo (22) SYN - 010 42 mg (19) | | | | | | | | | | | | | | Screen 1 7 14 21 28 35 42 49 56 63 70 77 84 Day CH 4 >10 ppm S
Slide 14: Monthly Responder as Defined by FDA
Monthly Responder as Defined by FDA • Monthly Responder* is an FDA recommended provisional primary endpoint in clinical trials for Irritable Bowel Syndrome with Constipation (IBS - C) • A Monthly Responder is defined as a subject who has a weekly response in at least 50% of the weeks of treatment du
Slide 15: Study 2: SYN-010 in IBS-C Patients
Study 2: SYN - 010 in IBS - C Patients, 12 Weeks of Treatment Dose Weeks 1 - 4 Dose Weeks 5 - 12 *Paired t - test vs Baseline (Day 1). a Subjects with unchanged dose had the smallest change from Study 1 to Study 2 15 SYN - 010 changes in IBS Symptom Severity Score vs study 1 baseline (day 1) SYN - 0
Slide 16: Study 2: SYN-010 in IBS-C Patients
Study 2: SYN - 010 in IBS - C Patients, 12 Weeks of Treatment 16 *Paired t - test vs Day 1; †Paired t - test vs Day 28. Error bars are SD. Week 4 | 8 | 12 Week 4 | 8 | 12 Week 4 | 8 | 12 Week -- | 8 | 12 *P=0.0001 † P=0.0006 *P=0.04 *P=0.001 † P=0.005 *P<0.0001 † P=0.0008 *P<0.0001 † P=0.001 *P=0.00
Slide 17: Study 1: Use of Rescue Medication
Study 1: Use of Rescue Medication Lower use of rescue medication for SYN - 010 vs. placebo ( mITT ) *p=0.013 vs Placebo † p =0.03 vs Placebo Fisher’s exact test % Subjects using RLax ® ( bisacodyl ; 5 mg) in Study 1 4/22* 4/19 † 12/22 Daily use of RLax ® ( bisacodyl ; 5 mg) in Study 1 >60% Less Resc
Slide 18: Inverse correlation between breath methane AUC and bowel movements
1 Study 2: SYN - 010 in IBS - C Patients, 12 Weeks of Treatment Inverse correlation between breath methane AUC and bowel movements CSBMs SBMs Data are for all subjects at Week 12 (at least 8 weeks of SYN - 010 42 mg) Data are for all IBS - C patients at Week 12 (at least 8 weeks of SYN - 010 42 mg)
Slide 19: SYN-010 Monthly Response Rate Components
19 SYN - 010 Monthly Response Rate Components % Responders increased over time when transferred to SYN - 010 42 mg Study 1 (Randomized) Study 2 (Open Label) Δ Study 1 → 2 Dose Week 4 Dose Week 8 Week 12 Week 8 - Week 4 % Subjects With Increase of ≥1 CSBM per Week vs Baseline Placebo 21 mg 42 mg 24%
Slide 20: SYN-010 Comparison to Competitor Therapies
20 SYN - 010 Comparison to Competitor Therapies SYN - 010 has a similar overall response rate* without causing diarrhea Drug Overall Response* Defined as ≥30% decrease in weekly average abdominal pain score AND an increase in ≥1 CSBM per week vs baseline in ≥50% of the weeks of treatment. *Response
Slide 21: SYN-010 Does Not Result in Adverse Changes to Lipid Profiles
21 Study 2: SYN - 010 in IBS - C Patients, 12 Weeks of Treatment SYN - 010 does not result in adverse changes to lipid profiles Dose Days 1 - 28 Dose Days 29 - 84 Triglycerides Cholesterol LDL - C SYN - 010 Dose Baseline Value (mean ± SD [n] mmol /L) Days 1 - 28 / 29 - 84 Cholesterol LDL - C Triglyc
Slide 22: SYN-010's Strategic Patent Position
Patented Methods of Treatment (Broadest Indication) Expires 2023 Patented and Pending Methods of Treating Constipation with SYN - 010 in Screened Patients Expires 2034 Pending Patent Applications on SYN - 010 Formulations, Methods of Use in Specific Patient Populations, and Clinical Dosing Expires 2
Slide 23: SYN-004: Prevention of C. difficile Infection and AAD
SYN - 004 Prevention of C. difficile Infection and AAD
Slide 24: Collateral Damage Caused by Antibiotic Use
Collateral Damage Caused by Antibiotic Use • Antibiotics • Prevent/treat primary infections • Carried to liver, transported to bile and excreted via large intestine • May unintentionally upset natural balance of gut microbiome by killing off good bacteria • May create a environment in the gut conduc
Slide 25: C. difficile Infections (CDI)
C. difficile Infections (CDI) Preventing CDIs is a national priority 1 Leffler DA et al. N Engl J Med 2015; 372:1539 - 1548. 2 (APIC) National Prevalence Study of Clostridium difficile in U.S. Healthcare Facilities. November 11, 2008. 3 Louie TJ, et al. N Engl J Med 2011;364:422 – 31. 4 Cornely OA,
Slide 26: Public Policy Tailwind
Public Policy Tailwind Global concern is growing around the spread of antibiotic resistance Gain Act - 2012 • Fast - Track, Priority Review, +5 - yr 21 st Century Cures Act – 2015 • Smaller Trials, Limited Populations DISARM Act* - 2015 • Medicare Reimbursement March 2015 National Action Plan • Comb
Slide 27: Paradigm Shift
Paradigm Shift Fewer CDIs expected with co - administration of SYN - 004 Treatments • β - lactam • Fluoroquinolone • Clindamycin • Other • Metronidazole • Vancomycin • Fidaxomicin SYN - 004 Paradigm SYN - 004 + beta - lactam antibiotics* SYN - 004 designed to protect the natural balance of the gut m
Slide 28: SYN-004 Co-Administered with Certain IV Antibiotics
SYN - 004 Co - Administered with Certain IV Antibiotics Designed to neutralize beta - lactam antibiotics in GI tract SYN - 004 Antibiotic To view the SYN - 004 mechanism of action video, please visit: http://www.syntheticbiologics.com/SYN - 004 1. SYN - 004 is an oral enzyme tablet (blue) to be co -
Slide 29: SYN-004 Protects the Microbiome from Antibiotic Damage
SYN - 004 Protects the Microbiome from Antibiotic Damage SYN - 004 prevented ceftriaxone - mediated changes in pig fecal microflora 29 Heat map shows log relative abundance of microbial genes in pig feces. Each square represents a microbial species present in an individual microbiome. Day 8 vs Day -
Slide 30: SYN-004 Phase 2a Proof-of-Concept Clinical Trial
Header: Calibri (Body) – font 27 Sub - header: Calibri (Light) – font 22 SYN - 004 Phase 2a Proof - of - Concept Clinical Trial Ceftriaxone intestinal chyme concentrations - study 1, periods 1 and 2 (n=8*) 2 ¹ For subjects 1006 and 1011 (not shown), SYN - 004 was detected later in their chyme (6.5 a
Slide 31: SYN-004 Phase 2a: Ceftriaxone Plasma Concentrations
SYN - 004 Phase 2a Proof - of - Concept Clinical Trial Ceftriaxone plasma concentrations (ng/ml) vs. time ( hrs ) 31 The ceftriaxone concentration in plasma was determined by a validated LC/MS - MS method. Assay LLOQ = 100 ng/ml Study 1 (n=10) Study 2 (n=14) Mean ceftriaxone concentration vs. time p
Slide 32: SYN-004 Phase 2b Proof-of-Concept Trial Design
SYN - 004 Phase 2b proof - of - concept trial design (ongoing) 32 ~75 Global Clinical Sites ~370 patients SYN - 004 + Ceftriaxone Placebo + Ceftriaxone Primary Endpoint: • Prevention of CDI and C. difficile associated diarrhea (CDAD) Secondary Endpoint: • Prevention of AAD* Exploratory Endpoint: • E
Slide 33: SYN-004: Strong Patent Position
33 Patented SYN - 004 Composition of Matter Expires 2031 Patented Other Beta - Lacatamase Composition of Matter and Uses Expires 2035 Pending Patent Applications on SYN - 004 Methods of Manufacture, Clinical Dosing and Formulation, Methods of Treatment, etc. Expires 2035/2036 Patents : ~40 U.S. and
Slide 34: SYN-004: Market Potential
SYN - 004: Market Potential Intended to target certain IV beta - lactam antibiotics * Estimate based on the following assumptions: Cost of SYN - 004/day of $100 x 117M days of “SYN - 004 target” β - lactam antibiotics in 2014 1 - Arlington Medical Resources (AMR), a Decision Resources Group Company,
Slide 35: Financial Highlights
Financial Highlights = Don
Slide 36: Financial Snapshot
Financial Snapshot • Cash balance (as of 3/31/16): ~$15.1 million • Current Price: $1.83 (as of 6/20/16) • 52 Week Range: $0.93 - $4.32 • Average Volume (3 months): 1,081,550 • Shares Outstanding: ~91 million (as of 3/8/16) • Options Outstanding: ~8.9 million* • Warrants Outstanding: ~7.9 million**
Slide 37: Company Highlights
Company Highlights • Advancing and developing gut microbiome therapeutics while targeting pathogen - specific diseases • Two lead microbiome - focused, billion - dollar market, potential drug candidates in Phase 2 • SYN - 010 is the only therapeutic in development that targets etiology of IBS - C sy
Slide 38: Milestones: Achieved & Upcoming
Milestones: Achieved & Upcoming Therapeutic Area/Product Candidate Timeline IBS - C – SYN - 010: Phase 2 (1 st study; acute, placebo - controlled) 2Q 2015 – Initiated Phase 2 4Q 2015 – Reported Phase 2 topline data Phase 2 (2 nd study; extension, SYN - 010 42mg) 4Q 2015 – Initiated Phase 2 1Q 2016 –
Slide 39: Investor Slide Deck June 2016
Investor Slide Deck June 2016 SYN – June 2016 Slide Deck (6.27.2016)
Synthetic Biologics — Investor Presentation (June 2016) on 6ix