Theriva Biologics, Inc. · AMEX:TOVX
Theriva Biologics — Synthetic Biologics — Investor Presentation (March 2016)
42 slides from Theriva Biologics's investor presentation, Mar 14, 2016
Slide 1: Investor Slide Deck March 2016
Investor Slide Deck March 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: Investment Considerations
Investment Considerations NYSE MKT: SYN • Lead candidates in Phase 2 development focused on protecting the gut microbiome while targeting pathogen - specific diseases • SYN - 010 = innovative approach to target an underlying cause of irritable bowel syndrome with constipation (IBS - C), not just the
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 – 2016 Therapeutic Area Proprietary Technology Product Candidate Discovery Preclinical Phase 1 Phase 2 Phase 3 IBS - C Oral
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: Diseases Directly Influenced by the Gut Microbiome
Source: Genome Medicine 2011, 3 :14 http://genomemedicine.com/content/3/3/14 Diseases Directly Influenced by the Gut Microbiome 7
Slide 8: Human Microbiome
Human Microbiome The body has 10 times as many microbe cells as human cells Source: http://commonfund.nih.gov/hmp/overview.aspx Human Microbiome > 1,000,000 Genes Human Genome 23,000 Genes 99% of Genes in the body are Microbial, NOT Human Leveraging the microbiome could significantly change medicine
Slide 9: Human Microbiome Over Time
Source: 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 Over Time Response to environmental conditions and life stages 9
Slide 10: Treatment of IBS-C
SYN - 010 Treatment of IBS - C
Slide 11: Pathogen-Specific Microbiome Therapeutic
Pathogen - Specific Microbiome Therapeutic Treating the underlying cause not symptoms SYN APPROACH: Anti - Archaea specific therapeutic 11
Slide 12: 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 of many bacterium that ferments carbohydrates in the gut which releases H 2 and CO 2 Carbohydrates Methanobrevibacter smithii archea c
Slide 13: Phase 2 trial design for IBS-C
SYN - 010 Phase 2 trial design for IBS - C – multiple sites in U.S. ~60 patients SYN - 010 High Dose 20 patients SYN - 010 Low Dose 20 patients Placebo 20 patients SYN - 010 High Dose 54 patients* Study #1 – 4 Week Acute Treatment Study #2 – 8 Week Extension Treatment Topline Analysis Study #1 Topli
Slide 14: Monthly responders in IBS-C patients
SYN - 010 in IBS - C Patients 12 Weeks of Treatment Increased % of Monthly Responders with time & in placebo transferred to SYN - 010 14 0% 10% 20% 30% 40% 50% Placebo (Wk 1-4) SYN-010 42 mg (5-12) SYN-010 21 mg SYN-010 42 mg SYN-010 42 mg SYN-010 42 mg All Subjects Combined Monthly Responders (%) R
Slide 15: SYN-010 Improves Symptoms in IBS-C Patients
SYN - 010 Improves Symptoms in IBS - C Patients Response frequency increased over time and in placebo transferred to SYN - 010* 15 Study Period % Weeks Subjects Had a Response Placebo / 42 mg 21 mg / 42 mg 42 mg / 42 mg Increase of ≥1 CSBM per Week vs Baseline Weeks 1 - 4 Weeks 5 - 8 Weeks 9 - 12 0%
Slide 16: Ongoing clinical trial development
SYN - 010 • Continued evaluation of SYN - 010 clinical pharmacokinetics • Determine dose(s) for advanced clinical testing • Submitted two Type C Meeting requests with FDA • Chemistry, Manufacturing, & Controls meeting (1H 2016) • Clinical meeting to confirm 505(b)(2) clinical pathway (1H 2016) • Req
Slide 17: IBS Market Overview
IBS Market Overview Source: IMS Audited Sales Data, Midas Global Sales (Analytics Link) 17 2015 IBS Global Therapeutic Sales Forecast ~$669.3M Global IBS Sales in 2023 are expected to be greater than $1.5B Market growth attributed to: • Increased uptake of Linzess ® and label expansion of Xifaxan ®
Slide 18: IBS-C Market Overview
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 underlying
Slide 19: Intellectual Property Strategy
SYN - 010 Intellectual Property Strategy
Slide 20: Foundational Patents
Foundational SYN - 010 Patents Exclusively licensed from Cedars - Sinai 20 Patented Methods of Treatment (Broadest Indication) Expires 2023 • U.S. Patent No. 9,192,618 Claim 1 : A method of treating IBS - C, comprising administering an effective amount of a selective inhibitor of methanogenesis to t
Slide 21: Specific Treatment Patent Family
SYN - 010 Specific Treatment Patent Family Exclusively licensed from Cedars - Sinai 21 • Allowed in U.S. and soon to issue (US 14/211,197) Claims cover t reating c onstipation with statins in patients h aving s tool m ethanogen l evels w hich are indicative of d isease • Patent application is being
Slide 22: Formulation Compositions Patent Family
SYN - 010 Formulation Compositions Patent Family Co - owned with, and exclusively licensed from, Cedars - Sinai 22 • Patent applications r ecently f iled • Pending in U.S. and PCT ( i.e. can b e f iled b roadly internationally) • Future patents expected to cover SYN - 010 formulations (Composition o
Slide 23: Minimally Absorbed in Canine Model
SYN - 010 Minimally Absorbed in Canine Model Mean concentration vs time (beta - hydroxyacid ; n=5) 23 0.0 5.0 10.0 15.0 20.0 25.0 0 4 8 12 16 20 24 28 32 36 40 Mean lovastatin ß - hydroxyacid (ng/mL) Time (h) 6 x pH 5.5 minitablets (42 mg) 6 x pH 7.0 minitablets (42 mg) 1 x pH 5.5 + 5 x pH 7.0 minit
Slide 24: Plasma Concentration
SYN - 010 Plasma Concentration • After 28 days of treatment, 65% of patients had no detectable plasma trough levels of lovastatin lactone or lovastatin beta - hydroxyacid • In the few patients with detectable trough levels at Day 28, concentrations of both lactone and beta - hydroxyacid were signifi
Slide 25: SYN-010's Strategic Patent Position
SYN - 010 Phase 2 Trial Completion/Phase 3 Initiation Projected ~2016 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
Slide 26: Prevention of C. difficile Infection and AAD
SYN - 004 Prevention of C. difficile Infection and AAD
Slide 27: 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 • A microbial imbalance in the gut microbiom
Slide 28: 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 29: 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 30: 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 31: Completed and ongoing clinical trials
SYN - 004 • First generation candidate, P1A, was evaluated in four Phase 1 and one Phase 2 clinical trials conducted in Europe • In total, 112 patients and 143 healthy normal subjects participated in the studies • Completed Phase 1a (40 participants) and 1b (24 participants) trials • PK data support
Slide 32: 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 Endpoints: • Prevention of AAD* Interim Analysis of Blind
Slide 33: Ongoing clinical trial development
SYN - 004 • FDA Type C Meeting requested (trial design and endpoints) • Phase 3 trial vision • Prevention of CDI and AAD among hospitalized patients receiving IV ceftriaxone and other beta - lactam antibiotics • Global study; multiple indications for IV beta - lactam therapy • Demonstrate no effect
Slide 34: Broad patent estate
SYN - 004 • ~35 U.S. and foreign patents; ~30 U.S. and foreign patents pending • Composition of matter claims and pharmaceutical compositions of beta - lactamases, including SYN - 004, was issued in November 2014 (U.S. Patent 8,894,994) • Carries a term to at least 2031 • An extensive portfolio of g
Slide 35: 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 36: C. difficile Market Overview
C. difficile Market Overview 1 SYN - 004 is a prophylactic approach vs treatment Currently the only methods for preventing primary C. difficile infection are through antibiotic stewardship and infection control 1 Not a comprehensive list of pipeline products; representative of compounds that are the
Slide 37: Financial Highlights
Financial Highlights _— A
Slide 38: Financial Snapshot
Financial Snapshot • Cash balance (as of 12/31/15): ~$20.8 million • Current Price: $1.87 (as of 3/7/16) • 52 Week Range: $0.93 - $4.32 • Average Volume (3 months): 1,190,070 • Shares Outstanding: ~91 million (as of 3/7/16) • Options Outstanding: ~8.9 million* • Warrants Outstanding: ~7.9 million**
Slide 39: Investor Slide Deck March 2016
Investor Slide Deck March 2016 SYN – Mar 2016 Slide Deck (3.14.2016) – FINAL - FINAL
Slide 40: Appendix: Phase 2 Clinical Trial Information
Appendix SYN - 010: Phase 2 Clinical Trial Information
Slide 41: Phase 2 Study 1 results
SYN - 010 • Treatment period completed in December 2015 (63 patients) • Primary endpoint was the change from baseline in the area under the curve (AUC) of breath methane production at Day 7, based on a 180 - minute lactulose breath test (LBT) • A necessary normalization of the severely left - skewed
Slide 42: Phase 2 Study 2 results
SYN - 010 • Treatment period completed in January 2016 (54 patients) • Met primary endpoint of evaluating the ability of SYN - 010 to sustain reduction in breath methane levels • Topline data from all patients who completed clinical trial showed a statistically significant decrease in methane produc
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