Synthetic Biologics Announces Detailed Data from Two SYN-010 Phase 2 Clinical Trials for the Treatment of Irritable Bowel Syndrome with Constipation (IBS-C)

ROCKVILLE, Md., May 23, 2016 /PRNewswire/ -- Synthetic Biologics, Inc. (NYSE MKT: SYN), a clinical stage company focused on developing therapeutics to protect the gut microbiome, reported detailed data supporting positive clinical outcomes from two previously reported Phase 2 clinical trials of its proprietary SYN-010 product candidate for the treatment of irritable bowel syndrome with constipation (IBS-C). Data from both trials were presented by Mark Pimentel, MD, FRCP(C), Director of the GI Motility Program and Laboratory at Cedars-Sinai, during a poster session yesterday at Digestive Disease Week® (DDW® 2016) in San Diego, CA. Synthetic Biologics will host a conference call today at 8:30 a.m. (EDT) to recap clinical results from both Phase 2 clinical trials of SYN-010, the Company's proprietary, modified-release formulation of lovastatin lactone designed to reduce methane production in the gut to treat an underlying cause of IBS-C.

"Results from the first and second Phase 2 clinical trials of SYN-010 presented during DDW® 2016 continue to suggest the potential ability of both the 21 mg and 42 mg dose strengths of SYN-010 to lower breath methane in IBS-C patients and treat an underlying cause of the abdominal pain and bloating associated with this disease," said Dr. Pimentel. "Unlike current treatments which are focused on relieving symptoms, outcomes from these latest SYN-010 studies strongly suggest a potential role for SYN-010 in treating an underlying cause of IBS-C by reducing the production of methane in the gut and improving the quality of life for IBS-C patients."

The two SYN-010 Phase 2 clinical trials are comprised of a randomized, double-blind, placebo-controlled, 4-week study comparing SYN-010 21 mg and 42 mg dose strengths to placebo (Study 1), followed by an open-label study in which eligible patients who completed Study 1 received SYN-010 42 mg for an additional 8 weeks (Study 2). The two Phase 2 SYN-010 clinical trials evaluated the change from baseline (Day 1 of Study 1) in breath methane, stool frequency and abdominal pain and bloating at the end of weeks 1, 4, 8 and 12 (Study 2 – Day 84) in patients diagnosed with IBS-C and with breath methane levels greater than 10 parts per million (ppm) at screening. Clinical data from patients who completed Study 1 (n=63) and Study 2 (n=54) showed clinically meaningful improvements in measurable endpoints, including:

• An increase from Study 1 baseline (Day 1) to the end of Study 2 (Day 84) in the percentage of patients identified as Monthly Responders, an FDA-defined composite measure incorporating improvements in CSBMs and abdominal pain¹:
  • Placebo / SYN-010 42 mg: 46%
  • SYN-010 21 mg / SYN-010 42 mg: 47%
  • SYN-010 42 mg / SYN-010 42 mg: 33%
    
• A clinically meaningful reduction from Study 1 baseline (Day 1) to the end of Study 2 (Day 84) in the IBS-Symptom Severity Score (IBS-SSS), which includes abdominal pain, bloating, stool frequency and quality of life scores:
  • Placebo / SYN-010 42 mg: p<0.004
  • SYN-010 21 mg / SYN-010 42 mg: p<0.001
  • SYN-010 42 mg / SYN-010 42 mg: p<0.001

Data analyzed from all patients who completed Study 1 and Study 2, and who were administered the 42 mg dose of SYN-010 for at least 8 weeks, demonstrated an inverse correlation (p-value=0.026) between breath methane area under the curve (AUC) and complete spontaneous bowel movements (CSBM). A similar inverse correlation (p-value=0.003) was observed between breath methane AUC and spontaneous bowel movements (SBM). Clinical data from Study 1 demonstrates that patients in both the 21 mg and 42 mg SYN-010 treatment groups used 60% less rescue medication (bisacodyl; 5 mg) when compared to placebo. SYN-010 was well tolerated in both Study 1 and Study 2 patients, and the few reported adverse events (AE) were balanced between groups. One mild incidence of diarrhea was reported during both studies and identified by the investigator as unrelated to SYN-010. No severe adverse events (SAEs) were reported.

"We are excited about the results of these clinical trials and are very enthusiastic about the potential for SYN-010 to be a best-in-class IBS-C therapeutic. We appreciate the contributions of the patients, investigators and committed staff who participated in these trials, and we look forward to continuing our clinical progress with the goal of making SYN-010 commercially available to the millions of patients suffering from this disease," said Jeffrey Riley, President and Chief Executive Officer. "During an advisory board meeting held this weekend at DDW®, we received valuable feedback from IBS-C and GI key opinion leaders which we intend to incorporate into the end of Phase 2 meeting with the FDA expected this summer. We also remain on track to initiate our Phase 3 clinical program for SYN-010 for the treatment of IBS-C later this year."

SYN-010 Pharmacokinetic Study in Healthy Human Volunteers

A separate, recently completed randomized, open-label clinical study of healthy volunteers evaluated the pharmacokinetic (PK) profile of the active ingredient of SYN-010, lovastatin lactone and its beta-hydroxyacid metabolite which is responsible for lowering cholesterol. Single 21 mg, 42 mg or 84 mg doses of SYN-010 were administered to three groups of eight fasted volunteers, once a day for each of four days. Plasma concentrations of lovastatin lactone and its beta-hydroxyacid metabolite were measured on Day 1 and Day 4. Plasma concentration vs. time profiles for lovastatin lactone and its beta-hydroxyacid metabolite, following administration of the first dose of all three dose strengths of SYN-010, showed a significant lag before first measurable concentrations were observed, followed by gradually increasing plasma levels of each component over the 24-hour analysis period. PK parameters were dose proportional and concentrations of SYN-010 reached a steady state by Day 4 of administration. Plasma levels of the beta-hydroxyacid metabolite were approximately half of those reported in the literature for similar doses of currently approved lovastatin products. The PK data in healthy volunteers support the modified-release profile of SYN-010 which is designed to avoid drug release in the stomach and deliver the antimethanogenic drug form, lovastatin lactone, into the lower small intestine and colon while reducing systemic exposure to the cholesterol-lowering lovastatin beta-hydroxyacid metabolite.

Conference Call

Synthetic Biologics' management will host a conference call today, Monday, May 23, 2016 at 8:30 a.m. (EDT), along with featured guest speaker, Dr. Mark Pimentel. Dr. Pimentel intends to recap the SYN-010 Phase 2 clinical trial data following the poster presentation at DDW® 2016 on Sunday, May 22, 2016 in San Diego. The dial-in information for the call is as follows:

U.S. toll free: 1-888-347-5280   
International: +1 412-902-4280

Participants are asked to dial in 15 minutes before the start of the call to register. The call and associated slide presentation will be webcast over the Internet at https://www.webcaster4.com/Webcast/Page/1096/14387. An archive of the call will be available for approximately six months at the same URL https://www.webcaster4.com/Webcast/Page/1096/14387 beginning approximately one hour after the call's conclusion. Slides associated with this conference call were filed with the SEC earlier today and are available on the investors section of our website www.syntheticbiologics.com.

About Synthetic Biologics' Two Phase 2 Clinical Trials of SYN-010

In the first four-week Phase 2 clinical trial of SYN-010, 63 patients with IBS-C and a breath methane value > 10 parts per million at screening were randomly assigned to receive placebo, a 21 mg SYN-010 dose or a 42 mg SYN-010 dose orally once daily for 28 days at multiple centers. The primary endpoint was the change from baseline in the AUC of breath methane production at Day 7, based on a 180-minute lactulose breath test (LBT). Secondary efficacy assessments included change in methane AUC at day 28, stool frequency and consistency, abdominal pain, and safety data.

Fifty-four patients, who completed the first Phase 2 clinical trial of SYN-010, rolled over into the second Phase 2 open-label clinical trial of SYN-010 which was conducted for an additional eight weeks at multiple centers. The primary endpoint of this extension study was to evaluate the sustainability of the effect of one daily dose strength (42 mg) of SYN-010 on breath methane production in breath methane-positive patients with IBS-C. Secondary endpoints included evaluation of the reduction in abdominal pain and bloating, the improvement in stool frequency and overall quality of life.

About SYN-010

SYN-010 is a proprietary, modified-release formulation of lovastatin lactone that is intended to reduce methane production by certain microorganisms (Methanobrevibacter smithii) in the gut while minimizing disruption to the microbiome to treat an underlying cause of IBS-C. SYN-010 is intended to act primarily in the intestinal lumen while avoiding systemic absorption, thereby targeting a major cause of IBS-C, not just the symptoms. To access the SYN-010 mechanism of action video on Synthetic Biologics' website, please click here.

About Synthetic Biologics, Inc.

Synthetic Biologics, Inc. (NYSE MKT: SYN) is a clinical stage company developing therapeutics to protect the gut microbiome while targeting pathogen-specific diseases. The Company's lead candidates in Phase 2 development are: (1) SYN-010 which is intended to reduce the impact of methane producing organisms in the gut microbiome to treat an underlying cause of irritable bowel syndrome with constipation (IBS-C), and (2) SYN-004 which is designed to protect the gut microbiome from the effects of certain commonly used intravenous (IV) beta-lactam antibiotics for the prevention of C. difficile infection and antibiotic-associated diarrhea (AAD). In collaboration with Intrexon Corporation, the Company is also developing preclinical stage monoclonal antibody therapies for the prevention and treatment of pertussis and novel discovery stage biotherapeutics for the treatment of phenylketonuria (PKU). For more information, please visit Synthetic Biologics' website at www.syntheticbiologics.com.

This release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. In some cases forward-looking statements can be identified by terminology such as "may," "should," "potential," "continue," "expects," "anticipates," "intends," "plans," "believes," "estimates," and similar expressions, and include statements regarding the potential ability of both the 21 mg and 42 mg dose strengths to lower breath methane in IBS-C patients, the potential role for SYN-010 in treating a major underlying cause of IBS-C by reducing the production of methane in the gut and improving the quality of life for IBS-C patients, the potential for SYN-010 to be a best-in-class IBS-C therapeutic, the continued clinical progress with the goal of making SYN-010 commercially available to treat IBS-C, timing of the interim analysis, the potential benefits of SYN-004 and SYN-010, timing of planned end of Phase 2 meeting with the FDA and initiation of Phase 3 development of SYN-010 and the market size. These forward-looking statements are based on management's expectations and assumptions as of the date of this press release and are subject to a number of risks and uncertainties, many of which are difficult to predict that could cause actual results to differ materially from current expectations and assumptions from those set forth or implied by any forward-looking statements. Important factors that could cause actual results to differ materially from current expectations include, among others, Synthetic Biologics' product candidates demonstrating safety and effectiveness, as well as results that are consistent with prior results, Synthetic Biologics' ability to initiate clinical trials and if initiated, to complete them on time and achieve desired results and benefits, Synthetic Biologics' clinical trials continuing enrollment as expected, Synthetic Biologics' ability to obtain regulatory approvals for commercialization of product candidates or to comply with ongoing regulatory requirements, regulatory limitations relating to Synthetic Biologics' ability to promote or commercialize its product candidates for specific indications, acceptance of its product candidates in the marketplace and the successful development, marketing or sale of Synthetic Biologics' products, Synthetic Biologics' ability to maintain its license agreements, the continued maintenance and growth of Synthetic Biologics' patent estate, Synthetic Biologics becoming and remaining profitable, Synthetic Biologics' ability to establish and maintain collaborations, Synthetic Biologics' ability to obtain or maintain the capital or grants necessary to fund its research and development activities, a loss of any of Synthetic Biologics' 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 and its other filings with the SEC, including subsequent periodic reports on Forms 10-Q and 8-K. The information in this release is provided only as of the date of this release, and Synthetic Biologics undertakes no obligation to update any forward-looking statements contained in this release on account of new information, future events, or otherwise, except as required by law.

¹ A Monthly Responder is defined as a patient who has a Weekly Response in at least 50% of the weeks of treatment during the month. A Weekly Responder is defined as a patient who experiences a decrease in weekly average score for worst abdominal pain in the past 24 hours of at least 30% compared with Study 1 Baseline and a stool frequency increase of 1 or more CSBM per week compared with Study 1 Baseline.

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