Intrexon Provides Update on Recent Stock Trading Activity
Published: Apr 22, 2016 7:15 a.m. ET
GERMANTOWN, Md., April 22, 2016 /PRNewswire/ -- Intrexon Corporation XON, -26.42% a leader in synthetic biology, provided an update to its shareholders regarding recent trading activity in the company's common stock. On Thursday, April 21, 2016, a materially false and misleading report regarding the company, its subsidiaries and its chairman and CEO was published on Seeking Alpha, a financial blog.
Intrexon does not, as a general matter, respond to blog posts, investor reports or analyst communications. In this case, however, Intrexon is providing this update given the inaccuracy of the report's content, the stated intent of the publisher to issue several more spurious reports in the coming days, and information received last night regarding the erroneous publication.
Yesterday evening, Intrexon received a draft report, dated December 2015, which contained similarly inaccurate claims and strikingly similar language, in some parts identical words, to that used in yesterday's report. Moreover, Intrexon received information that the source of the report was a particular hedge fund seeking to discredit Intrexon. The hedge fund, according to our information, desired to take a short position in the company's stock, was seeking a willing publisher of its report on the company, and intended to benefit from trading activity caused thereby.
Based on this information, Intrexon believes that it is the target of a campaign to manipulate trading in the company's securities, interfere with the company's business operations, and destroy the reputation of the company and its chairman and CEO. Intrexon, with the advice of counsel, is taking appropriate steps in light of these developments. In the meantime, we wish to assure our investors, collaboration partners, and employees that the company remains dedicated to advancing our business and to generating value for our shareholders.
Life Science Company of the Year
Immunomic Therapeutics, Inc.
Synthetic Biologics, Inc.
Winners to be Revealed May 11 at the Industry Awards Celebration
ROCKVILLE, Md., Mar 17, 2016 (BUSINESS WIRE) -- The Tech Council of Maryland (TCM), Maryland’s largest technology trade association, today announced the finalists for its 28 [th] Annual Industry Awards. Winners will be revealed at a celebration on May 11, 2016, at the Bethesda North Marriott Hotel & Conference Center. The event, which draws more than 800 executives from the technology and life science communities, celebrates individuals and companies that have made a significant impact in their sectors.
“For almost three decades, the Tech Council of Maryland has had the unenviable task of narrowing down the ever-growing list of innovative individuals and companies whose work has made an impact throughout the state and around the world,” said Phil Schiff, CEO, TCM. “We are honored to recognize this year’s finalists for their contributions to the fields of technology and life science.”
Finalists for the 2016 TCM Tech Awards are:
Chief Executive Officer of the Year – Life Science Company
Bill Hearl, CEO, Immunomic Therapeutics, Inc.
Jack Khattar, President and CEO, Supernus Pharmaceuticals
Kevin McRaith, CEO, WellDoc, Inc.
Chief Executive Officer of the Year – Technology Company
David Affeldt, CEO, GRSi
Ben Edson, Founder and CEO, VariQ
David Fout, CEO, Aquilent
Phillip Merrick, CEO, SparkPost
Financial Executive of the Year – Life Science Company
Mariam Morris, CFO, Cerecor Inc.
William Stevens, CFO, Personal Genome Diagnostics
Vit Vasista, CFO, REGENXBIO Inc.
Eric Winzer, CFO, Immunomic Therapeutics, Inc.
Financial Executive of the Year – Technology Company
Melissa Hook, CFO, Aquilent
Mitchell Paige, CFO, Dataprise
Life Science Company of the Year
Immunomic Therapeutics, Inc.
Synthetic Biologics, Inc.
Technology Company of the Year
Digital Infuzion, Inc.
Government Contracting Company of the Year
CALIBRE Systems, Inc.
Emerging Firm of the Year – Life Science Company
BrainScope Company, Inc.
Personal Genome Diagnostics
Emerging Firm of the Year – Technology Company
Axiologic Solutions LLC
TCM’s annual celebration will begin at 5:30 p.m. with a cocktail hour, followed by dinner and the awards ceremony. Sponsors include:
Award Sponsors – AstraZeneca/MedImmune, BDO, BioMarker Strategies, Capital One Commercial Banking, JLL, PwC, UBS Financial Services Inc. and VWR
Gold Sponsors – CDW, Immunomic Therapeutics, Iron Bow Technologies, Montgomery College, Novavax, Pillsbury Winthrop Shaw Pittman, Scheer Partners, Social & Scientific Systems and Sucampo
Silver Sponsors – MaxCyte, Psyadon Pharmaceuticals, The Meltzer Group and We Work for Health
Consumer Reports' new Ratings show many teaching hospitals fail to prevent this deadly disease
By Hallie Levine
Last updated: March 04, 2016
A life-threatening bacterial infection is gaining ground in America’s hospitals, according to a new report from the Centers for Disease Control and Prevention. And a Consumer Reports analysis finds that even some of the nation’s largest and most prestigious medical institutions are having a hard time getting it under control.
The infection, called C. diff (Clostridium difficile) sickened 101,074 hospital patients in 2014, the most recent data available, according to a March report from the CDC. Other research shows that overall about 450,000 people a year, inside and out of hospitals, are sickened by the infection, and it contributes to the death of about 29,000 people.
"New data show that far too many patients are getting infected with dangerous bacteria in healthcare settings,” said CDC director Tom Frieden, M.D. “Doctors and healthcare facilities have the power to protect patients—no one should get sick while trying to get well," he said.
While several serious hospital-acquired infections, such as those caused by central-line catheters, have declined in recent years, C. diff. rates increased by 4 percent between 2013 and 2014, according to the CDC.
And Consumer Reports’ updated Ratings of more than 3,200 hospitals across the country show that many are doing a poor job of reining in the infection. Overall, about a third of them received a low Rating in combating the infection. That means they have C. diff infection rates that are worse than the national benchmark.
That includes 24 of the nation’s largest teaching hospitals, including familiar ones such as Baylor University Medical Center in Dallas, the Cleveland Clinic in Cleveland, Cedars-Sinai Medical Center in Los Angeles, Johns Hopkins Hospital in Baltimore, and Mount Sinai Hospital in New York City. “Teaching hospitals are supposed to be places where we identify the best practices and put them to work,” said Lisa McGiffert, director of Consumer Reports' Safe Patient Project. “But even they seem to be struggling against this infection,” she said.
Synthetic Biologics, Inc. [SYN]
files SEC Form 8-K
Investor Slide Deck March 2016
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 can be identified by terminology such as "may," "should," "potential," "continue," "expects," "anticipates," "intends," "plans," "believes,“ "estimates,” “indicates,” and similar expressions . These statements are based upon management’s current beliefs, expectations and assumptions and are subject to a number of risks and uncertainties, many of which are difficult to predict and include statements regarding our timeline for our SYN - 004 and SYN - 010 clinical trials and reporting of data, the size of the market, benefits to be derived from use of SYN - 004 and SYN - 010 , our anticipated patent portfolio, and our execution of our growth strategy . The forward - looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those set forth or implied by any forward - looking statements . Important factors that could cause actual results to differ materially from those reflected in Synthetic Biologics’ forward - looking statements include, among others, our product candidates demonstrating safety and effectiveness, as well as results that are consistent with prior results, our ability to initiate clinical trials and if initiated, our ability to complete them on time and achieve the desired results and benefits, our clinical trials continuing enrollment as expected, our ability to obtain regulatory approval for our commercialization of product candidates or to comply with ongoing regulatory requirements, regulatory limitations relating to our ability to promote or commercialize our product candidates for the specific indications, acceptance of our product candidates in the marketplace and the successful development, marketing or sale of our products, our ability to maintain our license agreements, the continued maintenance and growth of our patent estate, us to becoming or remaining profitable, our ability to establish and maintain collaborations, our ability to obtain or maintain the capital or grants necessary to fund our research and development activities, a loss of any of our key scientists or management personnel, and other factors described in Synthetic Biologics’ annual report on Form 10 - K for the year ended December 31 , 2015 , subsequent quarterly reports on Form 10 - Qs and any other filings we make with the SEC . The information in this presentation is provided only as of the date presented, and Synthetic Biologics undertakes no obligation to update any forward - looking statements contained in this presentation on account of new information, future events, or otherwise, except as required by law . 2
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 symptoms • Intended to reduce impact of methane producing organisms in the gut • SYN - 004 = category creator for the prevention of C. difficile infection (CDI) and antibiotic - associated diarrhea (AAD) • Intended to degrade certain intravenous (IV) beta - lactam antibiotics in the gut • Targeting multi - billion dollar market opportunities addressing significant unmet medical needs • Multiple near - term and long - term clinical milestones • Experienced management team with extensive clinical and commercial track record 3
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 Pharmaceuticals, Inc., MedImmune , Inc., DynPort Vaccine • Raymond Stapleton, PhD, SVP, Manufacturing Merck & Co., Inc. • Michael Kaleko, MD, PhD, SVP R&D Genetic Therapy, Inc. (Novartis), Advanced Vision Therapies (currently known as Wellstat Ophthalmics ) • Klaus Gottlieb, MD, FACG, VP Clinical/Regulatory Quintiles, U.S. Food & Drug Administration • Maureen Early, MBA, VP Commercial Rhone Poulenc Rorer/Aventis, Upside Endeavors 4
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 modified - release lovastatin lactone SYN - 010 C Prevention of CDI and AAD [Degrade IV Beta - lactam Antibiotics] Oral enzyme SYN - 004 Prevention of CDI and AAD [Degrade Oral Beta - lactam Antibiotics] Oral enzyme SYN - 007 Prevention of CDI and AAD [Degrade IV Carbapenem Antibiotics] Oral enzyme SYN - 006 Prevention/Treatment of Pertussis (whooping cough) Monoclonal antibodies SYN - 005 I,T PKU Biotherapeutics SYN - 200 I Preserve gut microbiome and barrier/Treat inflammation Oral intestinal alkaline phosphatase SYN - 020
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 – Reported Phase 2 topline data Request end of Phase 2 Meeting with FDA Summer 2016 Pivotal Phase 3 trial(s) 2H 2016 – Initiate Phase 3 trial(s) CDI/AAD Prevention – 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 4Q 2015 – Reported supportive Phase 2a topline data Phase 2a open - label (2 nd ileostomy study; ceftriaxone + PPI) 2Q 2015 – Initiated Phase 2a 1H 2016 – Report Phase 2a topline data Phase 2b proof - of - concept ( double - blind, placebo - controlled) 3Q 2015 – Initiated Phase 2b trial 1H 2016 – Interim analysis of blinded data by independent monitor committee Pivotal Phase 3 trial(s) 2H 2016 – Initiate Phase 3 trial(s) 6
Source: Genome Medicine 2011, 3 :14 http://genomemedicine.com/content/3/3/14 Diseases Directly Influenced by the Gut Microbiome 7
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 8
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
SYN - 010 Treatment of IBS - C
Pathogen - Specific Microbiome Therapeutic Treating the underlying cause not symptoms SYN APPROACH: Anti - Archaea specific therapeutic 11
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 consumes hydrogen gas from Bacteroides and produces methane, which is lost from gut as “gas” Gas H 2 Source: http://commons.wikimedia.org/wiki/File:Intestine_and_stomach_ - _transparent_ - _cut.png 12
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 Topline Analysis Study #2 Primary Endpoint: • Reduction of breath methane Secondary Endpoints: • Reduction in abdominal pain and bloating • Increase in complete spontaneous bowel movement (CSBM) 12 Weeks *Study #1 completers rolled into Study #2 13
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 (%) Response improved when changed from Placebo to SYN - 010 Weeks 1 - 4|5 - 8|9 - 12 Weeks 1 - 4|5 - 8|9 - 12 Weeks 1 - 4|5 - 8|9 - 12 Weeks --- |5 - 8|9 - 12 Monthly Responders* had a Weekly Response in at least 50% of weeks A Monthly Responder is defined as a subject who has a weekly response in at least 50% of the weeks of treatment during the mo nth . A Weekly Responder is defined as a subject who experiences: 1. A decrease in weekly average score for worst abdominal pain in the past 24 hours of at least 30% compared with Study 1 Baseli ne, AND 2. A stool frequency increase of 1 or more complete spontaneous bowel movements per week compared with Study 1 Baseline
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% a 25% b 37.5% c 37.5% d 75% e 75% e 25% a 25% a 12.5 % b ≥30% Decrease in Abdominal Pain Score vs Baseline Weeks 1 - 4 Weeks 5 - 8 Weeks 9 - 12 0% b 50% f 75% g 0% d 50% e 75% e 0% a 100% a 100% f ≥30% Decrease in Bloating Score vs Baseline Weeks 1 - 4 Weeks 5 - 8 Weeks 9 - 12 0% b 50% f 75% g 25% d 75% e 100% e 25% a 100% a 100% f *Phase 2 clinical studies were not powered for statistical significance for this endpoint Data are medians (range 0 - 100%); No. of subjects a 17 b 16 c 14 d 20 e 19 f 15 g 13 Response criteria based on FDA approval endpoints for IBS - C No serious adverse events, and no related cases of diarrhea, were reported
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) • Request end of Phase 2 meeting with FDA (Summer 2016) • Designing Phase 3 clinical trial (ongoing) • Targeting Phase 3 initiation (2H 2016) Ongoing clinical trial development 16
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 ® • Launch of 4 late - stage pipeline products including 2 late - stage for IBS - C: ̶ Plecanatide - Synergy ̶ Tenapanor - Ardelyx $146.0 $141.9 $220.9 $61.4 $30.3 $68.8 rifaximin lubiprostone linaclotide alosetron ramosetron others
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 cause of IBS - C Treat symptoms Relieves constipation Relieves pain Causes more regular bowel movements Does not cause severe diarrhea h h h h h h h h h h h h *Based on preclinical data and Company expectations 1 Not a comprehensive list of pipeline products; representative of compounds that are the farthest along in clinical developmen t Source: www.clinicaltrials.gov ; GlobalData ; Corporate pipeline websites 18 h h
SYN - 010 Intellectual Property Strategy
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 the distal gut of a human patient in need thereof, wherein : the IBS - C is characterized by elevated intestinal methane levels and the selective inhibitor of methanogenesis is a HMG - CoA reductase inhibitor . • Patent application is being mined further in U.S. • Comparable patents granted in Europe, Canada, and Australia
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 m ined f urther in U.S. • Pending in Europe, Japan, China, Canada, Australia, Brazil and Mexico • U.S. Patent expires in 2034 and comparable t erm is expected in various international j urisdictions Patented and Pending Methods of Treating Constipation with SYN - 010 in Screened Patients Expires 2034
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 of Matter), among o thers , and have t erm to at least 2035 Pending Patent Applications on SYN - 010 Formulations, Methods of Use in Specific Patient Populations, and Clinical Dosing Expires 2035
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 minitablets (42 mg) Mevacor® (40 mg) Altoprev® (40 mg) One huge outlier Significantly reduced ß - hydroxyacid levels with pH 7.0 minitablets alone or in combination
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 significantly lower than observed for commercial lovastatin formulations • Consistent with limited absorption, there were no statistically significant changes in LDL - C levels relative to placebo after 28 days First Phase 2 clinical trial data 24
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 of Use in Specific Patient Populations, and Clinical Dosing Expires 2035 SYN - 010’s Strategic Patent Position 25 Patents : ~55 U.S. and Foreign Granted and ~15 U.S. and Foreign Pending Additionally, expected 3 Year New Use Marketing Exclusivity , measured from FDA Approval
SYN - 004 Prevention of C. difficile Infection and AAD
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 microbiome provides an opportunity for overgrowth of harmful pathogenic organisms (e.g., C. difficile ) which may cause severe diarrhea, damage to the colon and in some cases death Imbalance of the gut microbiome 24 million patients are administered IV antibiotics annually in the U.S. 1 1 - This information is an estimate derived from the use of information under license from the following IMS Health Incorporated inf ormation service: CDM Hospital database for full year 2012. IMS expressly reserves all rights, including rights of copying, distribution and repu blication. 27
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, et al. Lancet Infect Dis 2012;12:281 – 9. 5 Vardakas KZ, et al. Int J Antimicrob Agents 2012;40:1 – 8. 6 Lofgren ET et al. Epidemiology 2014; 25: 570 - 5. 7 Zimlichman E, et al. JAMA Intern Med 2013 8 https://www.whitehouse.gov/sites/default/files/docs/national_action_plan_for_combating_antibotic - resistant_bacteria.pdf ; 173 : 2039 - 46 . 28 #1 Most prevalent hospital - acquired infection in the U.S., according to the CDC 453,000 Number of patients infected with C. difficile annually 1 4 - 7 Number of extra days patients with C. difficile are hospitalized on average 2 25% Percentage of patients who experience a recurrence within 1 - 3 months 3 - 5 $1.5B Total cost of hospitalizations due to increasing annual expenditures related to C. difficile patients 6 - 7 29,000 Number of C. difficile - related deaths annually 8
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 microbiome during antibiotic use PREVENTION * I ntended to include penicillins plus cephalosporins Current Paradigm Antibiotics Treatments • β - lactam • Fluoroquinolone • Clindamycin • Other • Metronidazole • Vancomycin • Fidaxomicin C. difficile Infections (CDI) 29
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 - administered with IV antibiotics (yellow). 3. SYN - 004 is intended to remain in the GI tract and neutralize IV antibiotics (black), protecting the natural balance of the gut microbiome . 2. IV antibiotics can upset the natural balance of the gut microbiome , killing “good” bacteria, allowing for the overgrowth of C. difficile . 4. Co - administration of SYN - 004 is intended to allow the IV antibiotic (yellow) to treat the primary infection while protecting the gut microbiome (blue), and preventing CDI. 30
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 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 evaluable participants) • Demonstrated the ability of SYN - 004 to degrade ceftriaxone in the chyme of healthy participants with functioning ileostomies without affecting ceftriaxone in the bloodstream • Second Phase 2a trial (ongoing) • Characterize SYN - 004 activity on ceftriaxone in the small intestine in the presence of esomeprazole, an approved, OTC proton pump inhibitor Completed and ongoing clinical trials 31
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 Blinded Data by Independent Monitor Committee: • First 120 patients, and 10 cases of CDI • Evaluate baseline rate of CDI in placebo group 1:1 98 Patients enrolled as of 3/10/2016 *In addition to our primary and secondary endpoints, the Phase 2b study includes an exploratory endpoint to evaluate SYN - 004’s ability to potentially limit the disruption of gut microbiome diversity, also known as dysbiosis .
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 on blood levels of antibiotic or primary diagnosis cure rates Ongoing clinical trial development 33
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 granted use patents and pending patent applications for SYN - 004 - related technology • Additional patent filings covering composition of matter claims could extend patent protection of SYN - 004 to at least 2035 Broad patent estate 34
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, 2014 Audits of Acute Care Hospital Antibiotic Utilizat ion . 35 117M 16.7M 453K SYN - 004 Potential U.S. Market ~$12 Billion* 117M: Average days of SYN - 004 administered with target IV beta - lactam antibiotics 1 16.7M: Hospitalized patients 1 453K: New patients infected with C. difficile annually in the U.S.
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 farthest along in clinical developmen t Sources: www.clinicaltrials.gov ; GlobalData ; Corporate pipeline websites Product Candidate SYN - 004 * Dificid MK - 3451A ACAM - CDIFF™ SER - 109 PF - 06425090 Company Synthetic Merck Merck Sanofi Seres Pfizer Compound Enzyme to protect microbiome Macrocyclic antibiotic Monoclonal antibody Vaccine Microbiome therapeutic Vaccine Phase/Status Phase 2 Marketed Phase 3 Phase 3 Phase 2 Phase 2 Prophylactic/ Primary prevention Treatment N/A Prevention of recurrence N/A N/A N/A Route of administration Oral Oral Infusion Injections (3X over 30 days) Oral Injections (3X over 30 days) h h h h h *Based on preclinical & Phase 1 data and Company expectations 36
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** • Market Capitalization: ~$170 million • Headquarters in Rockville, Maryland * As of 12/31/2015 weighted average exercise price is $2.14 ** As of 12/31/2015 weighted average exercise price is $1.79 38
Investor Slide Deck March 2016 SYN – Mar 2016 Slide Deck (3.14.2016) – FINAL - FINAL
Appendix SYN - 010: Phase 2 Clinical Trial Information
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 breath test data, not prespecified in the statistical analysis plan, was accomplished by square root transformation; paired t - tests were performed allowing each subject to serve as their own control • SYN - 010 effects on breath methane were evaluated in a within group analysis by comparing the methane AUC on a LBT at Day 7 vs baseline Day 1 or Day 28 vs baseline Day 1 • After 7 days reductions in breath methane levels were seen in the 42 mg dose group (p=0.02) but not the 21 mg dose group (p=0.64) • In contrast, after 28 days both the 21 mg (p=0.03) and 42 mg (p=0.01) dose groups showed reductions in breath methane levels • Secondary efficacy assessments included change in methane AUC at Day 28, stool frequency and consistency, abdominal pain, and safety data • Preliminary analysis of secondary efficacy assessment data indicates that an improvement in the stool frequency response for the 21 mg dose group (p=0.02) was apparent, while the 42 mg dose group (p=0.54) was numerically better demonstrating a positive trend • Additionally, an improvement in weekly abdominal pain intensity for the 42 mg dose group (p=0.08) was seen, while the 21 mg dose group (p=0.26) was numerically better demonstrating a positive trend • There were no serious adverse events observed First Phase 2 clinical trial (4 week acute study) 41
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 production (p=0.002) • Measured from the beginning of the first Phase 2 study (Study 1 baseline - Day 1) to the end of the second Phase 2 study (12 weeks of treatment - Day 84) • Secondary endpoints included evaluating abdominal pain, bloating and CSBM • A statistically significant reduction in the mean IBS Symptom Severity Score (IBS - SSS; p
-- Conference Call Scheduled for Thursday, March 10, 2016 at 4:30 p.m. EST --
ROCKVILLE, Md., March 3, 2016 /PRNewswire/ -- Synthetic Biologics, Inc. (nyse mkt:SYN), a clinical stage company focused on developing therapeutics to protect the gut microbiome, intends to release its financial results for the year ended December 31, 2015 on Thursday, March 10, 2016, and to host a conference call the same day at 4:30 p.m. EST. The dial-in information for the call is as follows:
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Published: Mar 1, 2016 6:58 a.m. ET
-- New Allowances Bolster Strong SYN-004 Patent Estate --
ROCKVILLE, Md., March 1, 2016 /PRNewswire/ -- Synthetic Biologics, Inc. (nyse mkt:SYN), a clinical stage company focused on developing therapeutics to protect the gut microbiome, announced today that the U.S. Patent and Trademark Office (USPTO) issued Notices of Allowance for three patent applications which cover composition of matter claims and methods of protecting the gut microbiome from certain beta-lactam antibiotics for the prevention of C. difficile infection (CDI) and antibiotic-associated diarrhea (AAD). These new allowances further strengthen the Company's novel proprietary candidate, SYN-004, which is also covered by a composition of matter patent in the U.S.
SYN-004 is designed to degrade certain intravenous (IV) beta-lactam antibiotics excreted into the gastrointestinal (GI) tract to maintain the natural balance of the gut microbiome. C. difficile is associated with approximately 453,000 CDIs and 29,000 C. difficile-related deaths in the United States each year[i]. Upon issuance, these newly allowed applications reinforce Synthetic Biologics' extensive C. difficile-related patent estate, which includes approximately 35 U.S. and foreign patents and approximately 30 U.S. and foreign patent applications, and carry patent terms that extend from at least 2031 to 2035.
"These new patents will complement our growing SYN-004 patent estate and support our C. difficile prevention program, including two ongoing Phase 2 clinical trials," said Jeffrey Riley, President and Chief Executive Officer of Synthetic Biologics. "We're on schedule with respect to patient enrollment in our global Phase 2b proof-of-concept clinical trial intended to evaluate the ability of SYN-004 to prevent CDI and AAD in patients hospitalized with a lower-respiratory tract infection. During the first half of 2016, we also anticipate announcing topline data from the second Phase 2a clinical trial which is evaluating the ability of SYN-004 to degrade IV ceftriaxone in the presence of a proton pump inhibitor."