SYN-010

Overview

SYN-010 is a proprietary, modified-release formulation of lovastatin lactone that is intended to reduce methane production by certain microorganisms (M. smithii) in the gut while minimizing disruption to the microbiome to treat an underlying cause of irritable bowel syndrome with constipation (IBS-C).

Synthetic Biologics, Inc

Candidate Pipeline

Candidate & Indication Development Stage
Preclinical Phase 1 Phase 2 Phase 3 Market
SYN-010 Treatment of IBS-C
Preclinical Phase complete
Phase 1 Phase complete
Phase 2 Phase in progress
Phase 3 Phase not started
Market Phase not started

Differentiators/Key Benefits

SYN-010 is a proprietary, modified-release formulation of lovastatin lactone that is optimal for reducing methane-production by certain microorganisms (M. smithii) in the gut while minimizing disruption to the microbiome to treat an underlying cause of (IBS-C). Methane produced by M. smithii is perceived as an underlying cause of bloating, pain and constipation associated with IBS-C. SYN-010 is intended to act primarily in the intestinal lumen while avoiding systemic absorption, thereby targeting the cause of IBS-C, not just the symptoms.

Synthetic Biologics, Inc

How SYN-010 Works

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.

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Clinical Overview

Phase 2

  • 4 Week Acute Study
    • Treatment period completed for four week Phase 2 study in December 2015
    • This trial enrolled 63 patients with IBS-C and a breath methane value > 10 parts per million at screening who 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
    • The 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 area under the curve (AUC) on a lactulose breath test 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
    • For more information about this trial, please visit clinicaltrials.gov


  • 8 Week Extension Study
    • Treatment period completed for eight week extension Phase 2 clinical trial in January 2016
    • The primary endpoint of the extension Phase 2 is to evaluate the ability of SYN-010 to sustain the reduction in breath methane levels
      • Topline data from all patients who completed the second Phase 2 clinical trial of SYN-010 showed a statistically significant decrease in methane production (p=0.002) 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), thus meeting the study's primary endpoint
    • Secondary endpoints include evaluating abdominal pain, bloating and CSBM
      • A statistically significant reduction in the mean IBS Symptom Severity Score (IBS-SSS; p<0.0001), which includes abdominal pain, bloating, stool frequency and quality of life scores, for all patients from Study 1 baseline to the end of the second Phase 2 study
      • An increase in the percentage of patients identified as Monthly Responders, an FDA-defined composite measure incorporating improvements in CSBMs and abdominal pain1
    • There were no serious adverse events observed
    • For more information about this trial, please visit clinicaltrials.gov

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.

Market Need

10-15%

 

Percentage of population affected by IBS

45 Million

 

North Americans affected by IBS