Slide 1: New York City Microbiome Clinical Program Seminar
New York City Microbiome Clinical Program Seminar December 10, 2015
Slide 2: Introduction
Introduction Jeff Riley, President & Chief Executive Officer
Slide 3: Forward-Looking Statements
Forward - Looking Statements This presentation includes forward - looking statements on Synthetic Biologics’ current expectations and projections about future events . In some cases forward - looking statements can be identified by terminology such as "may," "should," "potential," "continue," "expec
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 .) • John Monahan, PhD, EVP R&D Avigen, Somatix, Triton B
Slide 5: Investment Considerations
Investment Considerations NYSE MKT: SYN • Clinical - stage therapeutics to protect the gut microbiome while targeting pathogen - specific diseases • Addressing multi - billion dollar market opportunities addressing significant unmet medical needs • Multiple near - term and long - term clinical miles
Slide 6: Microbiome Product Pipeline
Microbiome Product Pipeline C - Cedars - Sinai Medical Center collaboration Completed Planned – 2015 Therapeutic Area Product Candidate Discovery Preclinical Phase 1 Phase 2 Phase 3 C. difficile infection/ Antibiotic - associated diarrhea (AAD) SYN - 004 Irritable bowel syndrome with constipation (I
Slide 7: Milestones: Achieved & Upcoming
Milestones: Achieved & Upcoming Therapeutic Area/ Product Candidate Timeline C. difficile /AAD – SYN - 004: Phase 1a/1b 1Q 2015 – Positive topline Phase 1b results 1Q 2015 – Positive Phase 1a/1b PK data Phase 2a open - label (1 st ileostomy study; ceftriaxone) 1Q 2015 – Initiated Phase 2a 3Q 2015 –
Slide 8: What is a Microbiome?
Most microbiomes are essential for health; subtle, improper balance can cause disease Ubiquitous and Microscopic Essential for Health; Potential to Cure Disease The human microbiome can be considered a counterpart to the human genome (all of our genes ) Microbiomes cover every surface of the human b
Slide 9: The Microbiome and Disease: Impact of Modern Antibiotics
The Microbiome and Disease The impact of modern antibiotics Microbes living on and within the human body Most modern antibiotics kill both good microbes and the bad, stripping the body of friendly bacteria in the process of administration Death of ALL microbiomes – good and bad Antibiotics They may
Slide 10: The Microbiome and Disease: Disrupting the Microbiome
The Microbiome and Disease Disrupting the microbiome can have disastrous consequences http://learn.genetics.utah.edu/content/microbiome/disease/ A microbial imbalance in the gut microbiome provides an opportunity for overgrowth of harmful pathogenic organisms Interactions between microbes and the ce
Slide 11: 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
Slide 12: Joe Sliman, MD, MPH
Joe Sliman, MD, MPH Senior Vice President, Clinical & Regulatory Affairs • Senior Medical Director and Head of Patient Safety and Pharmacovigilance at Vanda Pharmaceuticals Inc . • Responsible for a New Drug Application for HETLIOZ ( tasimelteon ), which is indicated for the treatment of Non - 24 Ho
Slide 13: Klaus Gottlieb, MD, FACG
Klaus Gottlieb, MD, FACG Vice President, Clinical & Regulatory Affairs • Quintiles • Gastroenterology Therapeutic Area Lead • USFDA • Senior Clinical Reviewer, Division of Gastroenterology & Inborn Errors • Dr . Gottlieb’s responsibilities include: • Lead the Clinical Study teams through End - of -
Slide 14: Prevention of C. difficile Infection and Antibiotic-Associated Diarrhea / SYN-004
Prevention of C. difficile Infection and Antibiotic - Associated Diarrhea / SYN - 004 Joseph Sliman, M.D., MPH, SVP, Clinical & Regulatory Affairs
Slide 15: Professor Mark H. Wilcox, M.D., FRCPath
Professor Mark H. Wilcox, M.D., FRCPath C. difficile Keynote Speaker • Consultant / Head of Microbiology, Leeds Teaching Hospitals NHS Trust • Professor of Medical Microbiology, University of Leeds • Lead on C. difficile Infection, Public Health England • Chairman of Synthetic Biologics’ C. difficil
Slide 16: Professor Eric Sicard, MD
Professor Eric Sicard, MD C. difficile Keynote Speaker • Principal Investigator, Algorithme Pharma, Inc. • Family doctor and biologist with a strong interest for research and preventative medicine • Medical Director, Gamma Dynacare • Board Member, Tactio Medical Advisory Board • Principal Investigat
Slide 17: SYN-004 Clinical Development
SYN - 004 Clinical Development Mark Wilcox, MD. FRCPath , Leeds Teaching Hospitals NHS Trust
Slide 18: SYN-004 Clinical trial development to date
SYN - 004 • Completed Phase 1a (40 participants) and 1b (24 participants) trials • PK data supports SYN - 004 should have no effect on the antibiotic in the bloodstream • No clinically significant safety events were observed; well tolerated by participants • Completed first Phase 2a trial (10 evalua
Slide 19: SYN-004 Phase 2b Proof-of-Concept trial
• Initiated Phase 2b Proof - of - Concept trial in September 2015 • Evaluate the ability of SYN - 004 to prevent C. difficile infection (CDI) and antibiotic - associated diarrhea in patients admitted for LRTI receiving at least 5 days of IV ceftriaxone • Screening and enrollment in the U.S. and Cana
Slide 20: Phase 2b trial design and endpoints
20 ~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 • Limiting disruption of gut microbiome diversity 1:1 SYN - 004 Clinical trial developmen
Slide 21: SYN-004 First Phase 2a Clinical Trial Results
SYN - 004 First Phase 2a Clinical Trial Results Eric Sicard, MD, Algorithme Pharma, Principal Investigator
Slide 22: Unique approach to support mechanism of action
SYN - 004 Study SB - 004 - 01 - 003 • Study SB - 004 - 01 - 003 study was conducted in healthy volunteers with functioning ileostomy • Provided in vivo data that complements in vitro and nonclinical data to support the mechanism of action (MOA) of SYN - 004 • Following oral administration, SYN - 004
Slide 23: Study objectives
SYN - 004 Study SB - 004 - 01 - 003 • Primary : Evaluate the effect of two strengths of oral SYN - 004 (75 mg or 150 mg) administered twice in six hours on the chyme concentrations of ceftriaxone administered as an intravenous (IV) infusion • Secondary : • Compare ceftriaxone PK parameters in plasma
Slide 24: Study design
SYN - 004 Study SB - 004 - 01 - 003 • Randomized, multi - center, open - label study • Healthy subjects with functioning ileostomies between the ages of 18 and 80 years • Treatment Period 1: all subjects received an IV infusion of 1 gram (g) ceftriaxone. • Treatment Period 2: all subjects received a
Slide 25: Enrollment
SYN - 004 Study SB - 004 - 01 - 003 • Subjects enrolled: 11* • 8 males/Ages 23 - 74 • 3 females/Ages 52 - 62 • Subjects dosed with SYN - 004: 10 • Subjects completing study: 10 Enrollment * One subject withdrew from the study during period 1 ceftriaxone infusion due to an adverse reaction to the inf
Slide 26: Ceftriaxone Chyme Concentrations
Ceftriaxone Chyme Concentrations - Period 1 and Period 2 Without 2 outlier subjects (n=8) IV Ceftriaxone Infusion Oral SYN - 004 Dosage
Slide 27: Chyme Ceftriaxone Concentrations for Two Outlier Subjects
Chyme Ceftriaxone Concentrations for Two Outlier Subjects
Slide 28: Chyme SYN-004 Concentrations
Chyme SYN - 004 Concentrations A ll subjects
Slide 29: Plasma Ceftriaxone Concentration by Subject
Plasma Ceftriaxone Concentration by Subject n=10
Slide 30: SYN-004 Plasma Concentration
SYN - 004 Plasma Concentration • No SYN - 004 was detected in any plasma sample • Max dose 300 mg given as 150 mg twice 6 hours apart • LLOQ of the Assay is 0.8 ng/mL • Consistent with results from SAD and MAD studies n=10
Slide 31: Incidence of Treatment-Emergent Adverse Events
Incidence of Treatment - Emergent Adverse Events (TEAEs ) Considered Related To Study Drug by MedDRA Coded Terms In Period 2 -- Safety Population Treatment AB: Ceftriaxone + 75 mg SYN - 004 (N=6) Treatment AC: Ceftriaxone + 150 mg SYN - 004 (N=5) Total (N=11) Total # of Related TEAEs 2 1 3 Subjects
Slide 32: Outcomes
SYN - 004 Study SB - 004 - 01 - 003 • SYN - 004 reduced the ceftriaxone concentration in the intestinal chyme of subjects dosed with IV ceftriaxone and oral SYN - 004 • Ceftriaxone concentrations observed in Period 2 were reduced to near below or below detection limits in the chyme when both substan
Slide 33: Q&A Session
Prevention of CDI and AAD / SYN - 004 Q&A Session
Slide 34: Irritable Bowel Syndrome with Constipation (IBS-C)
Irritable Bowel Syndrome with Constipation (IBS - C) Joseph Sliman, M.D., MPH, SVP, Clinical & Regulatory Affairs
Slide 35: Mark Pimentel, MD, FRCP(C)
Mark Pimentel, MD, FRCP(C) IBS - C Keynote Speaker • Cedars - Sinai Medical Center • Director, GI Motility Program • Professor of Medicine • Serves as a principal investigator or co - investigator for numerous basic science, translational and clinical studies in IBS, and the relationship between gut
Slide 36: SYN-010 First Phase 2 Results
SYN - 010 First Phase 2 Results Mark Pimentel, MD, FRCP(C), Cedars - Sinai Medical Center
Slide 37: SYN-010 Safety and Efficacy in IBS-C Patients
SYN - 010 Safety and Efficacy in IBS - C Patients • Randomized, double - blind, parallel - group, placebo - controlled study in breath methane positive IBS - C patients • Patients dosed at 13 centers in the United States • Compared SYN - 010 21 mg and 42 mg with placebo • 28 days of single, daily do
Slide 38: Study overview
SYN - 010 Safety and Efficacy in IBS - C Patients SB - 2 - 010 - 001 Study overview Lactulose breath test CH 4 AUC (fasted) Single - point breath CH 4 (fasted) SYN - 010 21 mg q.d . (n=22) Placebo q.d . (n=22) SYN - 010 42 mg q.d . (n=19) | | | | | | | | | Screen 1 2 5 7 8 14 21 28 Study Day DD VS C
Slide 39: Inclusion and exclusion criteria
• Key Inclusion Criteria • IBS - C (modified Rome III) • Breath methane >10 ppm at Screening • Compliance with 7 - day Diary Screening • Discontinue laxatives, medications, supplements intended to treat constipation • Refrain from lifestyle changes that may affect IBS - C symptoms (e.g. new diet) •
Slide 40: Subject demographics
SYN - 010 in IBS - C Patients SB - 2 - 010 - 001 Subject demographics Placebo SYN - 010 21 mg SYN - 010 42 mg Female, n/total (%) 17/22 (77.3%) 19/22 (86.4%) 14/19 (73.7%) Age , years* 46.4 ± 10.3 42.6 ± 6.0 44.7 ± 9.5 Breath CH 4 , ppm*† 38 ± 20 39 ± 30 42 ± 28 Race, n (%) White 16 (72.7%) 21 (95.5
Slide 41: Measuring methane using the lactulose breath test
0.0 5.0 10.0 15.0 20.0 25.0 30.0 35.0 40.0 45.0 0 20 40 60 80 100 120 140 160 180 200 Breath Methane (ppm) Time (min) Subject A Subject B • Standardized measurement of methane production • Day 1, Day 7 and Day 28 prior to SYN - 010 dosing • Patient fasts overnight then provides a breath sample (Time
Slide 42: SYN-010 Reduced Breath Methane in IBS-C Patients
- 10.6 - 31.0 11.1 - 22.6 - 34.6 - 34.3 - 120 - 100 - 80 - 60 - 40 - 20 0 20 40 Change in Breath Methane AUC (ppm*h) Placebo SYN - 010 21 mg SYN - 010 42 mg SYN - 010 Reduced Breath Methane in IBS - C Patients Decrease from baseline in methane AUC ( mITT Population) p=0.64 p=0.88 p=0.02* p=0.15 p=0.
Slide 43: Improved Weekly Stool Frequency Response
16% 41% 22% 0% 10% 20% 30% 40% 50% 60% 70% 80% % Weeks Patients Had a Stool Response Placebo SYN - 010 21 mg SYN - 010 42 mg SYN - 010 Improved Weekly Stool Frequency Response Percentage of weeks subjects had a response ( mITT Population) *Statistically different from Placebo based an a Wilcoxon Man
Slide 44: Improved Weekly Abdominal Pain Response
11% 15% 29% 0% 10% 20% 30% 40% 50% 60% 70% 80% % Weeks Patients Had a Pain Response Placebo SYN - 010 21 mg SYN - 010 42 mg SYN - 010 Improved Weekly Abdominal Pain Response Percentage of weeks subjects has a response ( mITT Population) P=0.08† P=0.26† †P - value based an a Wilcoxon Mann - Whitney t
Slide 45: Effects on Combined Weekly Response
1% 7% 9% 0% 5% 10% 15% 20% 25% 30% % Weeks Patients Had a Weekly Response Placebo SYN - 010 21 mg SYN - 010 42 mg SYN - 010 Effects on Combined Weekly Response Trend to dose - dependent improvement ( mITT Population) †P - value based an a Wilcoxon Mann - Whitney test for the comparison of the SYN -
Slide 46: Dose-Response in IBS-C Patients
82% 14% 59% 41% 68% 32% 27% 73% 58% 42% 47% 53% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Abdominal Pain No Response (0% Weeks) Abdominal Pain Any Response (25 - 100% Weeks) Stool Frequency No Response (0% Weeks) Stool Frequency Any Response (25 - 100% Weeks) % of Patients with Response Placebo SY
Slide 47: Effects on Global Assessment of Improvement
16% 32% 29% 21% 25% 35% 21% 31% 50% 0% 10% 20% 30% 40% 50% 60% Placebo SYN - 010 21 mg SYN - 010 42 mg % IBS - GAI Responders Week 2 Week 3 Week 4 SYN - 010 Effects on Global Assessment of Improvement Improvement in IBS - GAI over time at 42 mg dose ( mITT Population) †p - value based an a Chi - squ
Slide 48: SYN-010 Well Tolerated in IBS-C Patients
SYN - 010 Well Tolerated in IBS - C Patients SB - 2 - 010 - 001 Treatment emergent adverse events (TEAEs) Placebo SYN - 010 21 mg SYN - 010 42 mg Withdrawals 2 2 2 Serious AEs 0 0 0 TEAEs 1 (4.5%) 1 (4.5%) 2 (10.5%) Type Gastroenteritis Headache 1. Elevated GGT 2. Elevated AST, CPK Severity Moderate
Slide 49: Summary of Clinical Outcomes to Date
SYN - 010 Summary of Clinical Outcomes to Date • SYN - 010 was well tolerated in breath methane positive IBS - C patients treated with single, daily, oral doses of 21 mg or 42 mg for 28 days • Only 3 TEAEs (7.3%) observed in SYN - 010 treated patients • SYN - 010 reduced breath methane in breath met
Slide 50: SYN-010 Development in IBS-C
SYN - 010 Development in IBS - C • SB - 2 - 010 - 001 complete data set to be reviewed • Data release Q1 2016 • 8 week extension study nearing completion • 54 patients from SB - 2 - 010 - 001 continued into an open - label 8 week extension study administering single, daily, doses of SYN - 010 42 mg.
Slide 51: IBS-C / SYN-010 Q&A Session
IBS-C / SYN-010 Q&A Session synthetic ()
Slide 52: Closing
Closing Jeff Riley, President & Chief Executive Officer
Slide 53: New York City Microbiome Clinical Program Seminar
New York City Microbiome Clinical Program Seminar December 10, 2015 SYN Microbiome Clin Prog Seminar (SYN Slides) - FINAL