Scientific Publications

SYN-004 (ribaxamase)

Protection of the Gut Microbiome - Prevention of C. difficile and Antibiotic-Associated Diarrhea

Papers

Kokai-Kun J et al. Characterization of Clostridium difficile isolates collected during a phase 2b clinical study with SYN-004 (ribaxamase) for the prevention of C. difficile infection. Anaerobe (2018)

Abstract

Connelly S, et al. Distinct consequences of amoxicillin and ertapenem exposure in the porcine gut microbiome. Anaerobe (2018)

Abstract

Bristol A et al. Formulation development of SYN-004 (ribaxamase) oral solid dosage form, a β-lactamase to prevent intravenous antibiotic-associated dysbiosis of the colon. Intl J Pharm 2017 Dec 20

FULL ARTICLE

Connelly S et al. SYN-004 (ribaxamase), an Oral Beta-Lactamase, Mitigates Antibiotic-Mediated Dysbiosis in a Porcine Gut Microbiome Model. J Appl Microbiol. 2017 Feb 28. DOI: 10.1111/jam.13432

Abstract

Kokai-Kun JF et al. The Oral β-Lactamase SYN-004 (Ribaxamase) Degrades Ceftriaxone Excreted into the Intestine in Phase 2a Clinical Studies. 41(3):e02197-16

Full Article

Kaleko M, et al. Development of SYN-004, an oral beta-lactamase treatment to protect the gut microbiome from antibiotic-mediated damage and prevent Clostridium difficile infection. Anaerobe 41 (2016)

Abstract

Roberts T, et al. Tolerability and Pharmacokinetics of SYN-004, an Orally Administered β-Lactamase for the Prevention of Clostridium difficile-Associated Disease and Antibiotic-Associated Diarrhea, in Two Phase 1 Studies. Clin Drug Investig. 2016 Sep

PubMed Abstract

Kokai-Kun JF et al. Nonclinical Safety Assessment of SYN-004: An Oral Beta-lactamase for the Protection of the Gut Microbiome From Disruption by Biliary-Excreted, Intravenously Administered Antibiotics. Int J Toxicol 2015 Dec 23.

PubMed Abstract

Crowther GS, Wilcox MH. Antibiotic therapy and Clostridium difficile infection-primum non nocere-first do no harm. Infection and drug resistance. 2015;8:333.

Full Article

Pitout JD. Ipsat P1A, a class A β-lactamase therapy for the prevention of penicillin-induced disruption to the intestinal microflora. Current Opinion in Investigational Drugs. 2009; 10(8):838-844.

PubMed Abstract

Tarkkanen A et al. P1A recombinant β-lactamase prevents emergence of antimicrobial resistance in gut microflora of healthy subjects during intravenous administration of ampicillin. Antimicrob Agents Chemother 2009; 53 (6): 2455-2462

Full Article

Stiefel U et al. Orally administered recombinant metallo- β-lactamase preserves colonization resistance of piperacillintazobactam treated mice. Antimicrob Agents Chemother. 2005; 49(12): 5190-5191.

Full Article

Harmoinen J et al. Orally Administered Targeted Recombinant Beta-Lactamase Prevents Ampicillin-Induced Selective Pressure on the Gut Microbiota: a Novel Approach to Reducing Antimicrobial Resistance. Antim Agents Chemother 2004; 48(1): 75-79.

Full Article

Harmoinen J et al. Enzymic degradation of a β-lactam antibiotic, ampicillin, in the gut: a novel treatment modality. J Antimicrob Chemother 2003; 51(2):361-365.

Full Article

Stiefel U et al. Oral administration of β-lactamase preserves colonization resistance of piperacillin-treated mice. Journal of Infect Dis 2003; 188: 1605-1609.

Full Article

Abstracts, Posters and Presentations

Wacher V et al. CDI has a (Prevention) Perception Problem: Lessons from the On-Going Development of SYN-004 (ribaxamase). C. diff Awareness Conference and Health Expo 2018.

Presentation

Kokai-Kun J et al. Preventing Hospital Acquired Infections – Review of Clinical Trials for Ribaxamase in the Prevention of Clostridium difficile Infections. World AMR 2018

Presentation

Lubarda J et al. A Clinical Practice Assessment on Clostridium difficile Infection. ID Week 2018

Poster

Kokai-Kun J et al. SYN-004 (ribaxamase) Protects the Gut Microbiome of Patients Treated with Ceftriaxone from Disruption and Reduces the Emergence of Antimicrobial Resistance. ID Week 2018

Poster

Connelly S. et al. Oral Beta-Lactamase Therapies Prevent Microbiome Damage and Attenuate Antibiotic Resistance from IV and Oral Antibiotics in Large Animal Models of Antibiotic-Mediated Gut Dysbiosis. ID Week 2018

Poster

Kokai-Kun J et al. SYN-004 (ribaxamase) Prevented Clostridium difficile Infection in Patients Being Treated with Beta-Lactam Antibiotics. ICDS 2018

Presentation

Lubarda J et al. C. difficile Prevention and Management: An Assessment of Current Clinical Practice Patterns of Physicians. ICDS 2018

Poster

Kokai_Kun J et al. SYN-004 (ribaxamase) Prevents Clostridium difficile Infection and Antimicrobial Resistance. Anaerobe 2018

Presentation

Connelly S et al. Protecting the Gut Microbiome from Antibiotics. Anaerobe 2018

Presentation

Furlan Freguia et al. Protecting the Gut Microbiome from Antibiotics. Microbiome Movement Drug Development Summit 2018.

Presentation

Kaleko M et al. Orally Delivered Beta-Lactamase Prevents Gut Microbiome Dysbiosis Caused by IV and Oral Antibiotics and Mitigates Propagation of Antibiotic Resistance in Porcine and Canine Models. DDW 2018.

Poster

Bristol A et al. Formulation Strategies for Solid Oral Drug Products to Prevent or Treat Diseases of the Gut Microbiome. Biologics Formulation and Drug Delivery Technologies Summit 2018.

Presentation

Kokai-Kun J et al. Protection of the Gut Microbiome: Innovative Solutions to Dysbiosis and Antibiotic Resistance. North American Microbiome Congress 2018

Presentation

Furlan Freguia C et al. Clinical Development of Ribaxamase, an Oral-Beta Lactamase Intended to Protect the Gut Microbiome and Prevent C. difficle Infection. Microbiome Drug Development 2018

Presentation

Kokai-Kun J et al. SYN-004 (ribaxamase) Protects the Diversity of the Gut Microbiome in Patients Receiving Intravenous Ceftriaxone Treatment. ID Week 2017

POSTER

Connelly S et al. Gut Antibiotic Inactivation by Beta-Lactamases is Intended to Prevent Microbiome Damage and Attenuate Antibiotic Resistance in Large Animal Models. ID Week 2017

Poster

Kaleko M et al. SYN-006, a Novel Carbapenemase, Intended to Protect the Gut Microbiome from Antibiotic-Mediated Damage, May Also Reduce Propagation of Carbapenem-Resistant Pathogens. ID Week 2017

Poster

Kokai-Kun J et al. SYN-004 (ribaxamase) prevents New Onset Clostridium difficile Infection by Protecting the Integrity Gut Microbiome in a Phase 2b Study. ID Week 2017

Presentation

Kokai-Kun J et al. SYN-004 (Ribaxamase), an Oral β-lactamase, Prevented Clostridium difficile Infection and Protected Patients from Colonization by Antimicrobial Resistant Pathogens by Preserving Gut Microbiome Diversity in a Phase 2b Clinical Trial. DDW 2017

Presentation

Connelly S et al. An Orally-Delivered Beta-Lactamase Protects the Gut Microbiome from Antibiotic-Mediated Damage and Mitigates Propagation of Antibiotic-Resistance Genes in a Porcine Dysbiosis Model. DDW 2017

Presentation

Connelly S, et al. SYN-004 (ribaxamase), a Beta-Lactamase, Protects the Gut Microbiome from IV Antibiotics and Reduces Propagation of Antibiotic-Resistance Genes in a Porcine Dysbiosis Model. ECCMID 2017

Poster

Kokai-Kun J et al. Advancing Gut Microbiome Therapeutics. ECCMID 2017

Poster

Connelly S, et all. Clinical-Stage, Oral b-Lactamase Enzyme to Prevent Clostridium difficile Infection Triggered by Antibiotic-Mediated Gut Microbiome Disruption. ID Week 2016.

POSTER

Donskey CJ, et all. Healthcare Facility-Associated Clostridium difficile Infection in Hospitalized Patients Receiving Intravenous Beta-Lactam Antibiotics in the Veterans Affairs Healthcare System. ID Week 2016.

POSTER

Kokai-Kun J, et al. The Oral β-Lactamase SYN-004 (ribaxamase), Designed to Protect the Gut Microbiome from Biliary Excreted IV Antibiotics, Efficiently Degrades Ceftriaxone in Two Phase 2a Clinical Trials. ID Week 2016

Poster

Connelly et al. Development of Orally-Delivered Therapeutics to Protect the Gut Microbiome from Antibiotic-Mediated Damage. ASM 2016.

Poster

Kokai-Kun J et al. SYN-004, an Oral β-lactamase to Prevent Clostridium difficile, Degrades Ceftriaxone Excreted in the Human Intestine in Phase 2a Clinical Trials. ASM 2016.

Poster

Gottlieb K et al. Oral Beta-Lactamase Therapy to Prevent Antibiotic-Induced Disruption of the Gut Microbiome. SHEA 2016.

Poster

Connelly S et al. SYN-004, a Clinical-Stage, Orally Delivered Beta-Lactamase Therapy Protects the Gut Microbiome from IV Antibiotics. ECCMID 2016.

Poster

Rufiange M et al. A Phase 1b/2a Randomized Open-label Study Measuring Chyme Concentrations of Intravenously Administered Ceftriaxone in the Presence of the Oral Beta-lactamase SYN-004. CDDW 2016.

Poster

Gottlieb K et al. Development of Clinical Stage Oral β-Lactamase Therapies Designed for the Prevention of Antibiotic-Induced Disruption of the Intestinal Microbiome. WAidid 2016.

Poster

Sliman J et al. Clinical Evaluation of SYN-004, an Oral Beta-Lactamase Therapy for the Prevention of Antibiotic-Induced Disruption of Intestinal Microflora. ASM 2015.

Abstract Poster

Connelly S et al. A Clinical Stage Oral Beta-Lactamase Therapy Prevents Antibiotic-Mediated Damage of the Gut Microbiome. ICAAC/ICC 2015.

Abstract Presentation

Connelly S et al. SYN-004, a Clinical Stage Oral Beta-Lactamase Therapy, Protects the Intestinal Microflora from Antibiotic-Mediated Damage in Humanized Pigs. DDW 2015.

Abstract Poster

Kaleko M et al. SYN-004, a Class A Beta-Lactamase Therapy for the Prevention of Antibiotic-Induced Disruption of Intestinal Microflora. IDWeek 2014.

Abstract & Poster

Kaleko M et al. P4A, a Novel Oral Beta-Lactamase for the Prevention of Cephalosporin-Induced C. difficile Infection. ICAAC 2014.

Abstract Poster

Connelly S et al. SYN-004, a Novel, Clinical-Stage Oral Beta-Lactamase Therapy to Protect the Microbiome from Antibiotic-Mediated Damage. Biochemical and Molecular Engineering XIX. July 2015.

Presentation

Connelly S et al. Novel Broad-Spectrum Beta-lactamase Therapy to Protect the Gut Microbiome from Antibiotics. ICETAR 2015.

Presentation

Connelly S et al. Development of Therapeutic Agents that Protect the Colonic Microflora from Beta-Lactam Antibiotics for the Prevention of Clostridium difficile Infection. ASM 2015.

Abstract Poster

Kokai-Kun J et al. SYN-004, A Novel Strategy to Protect the Gut Microbiome from the Deleterious Effects of Residual IV Beta-Lactam Antibiotics. 3rd World Congress on Targeting Microbiota. October 2015.

Abstract Presentation

SYN-010

Treatment of Irritable Bowel Syndrome with Constipation (IBS-C)

Papers

Muskal SM et al. Lovastatin lactone may improve irritable bowel syndrome with constipation (IBS-C) by inhibiting enzymes in the archaeal methanogenesis pathway. F1000Research 2016, 5:606

Full Article

Gottlieb K et al. Review article: inhibition of methanogenic archaea by statins as a targeted management strategy for constipation and related disorders. Aliment Pharmacol Ther. 2015 Nov 11.

Epub ahead of print

Pimentel M et al. Gas and the Microbiome. Curr Gastroenterol Rep. 2013 Dec;15(12):356.

PubMed Abstract

Basseri RJ et al. Antibiotics for the treatment of irritable bowel syndrome. Gastroenterology & Hepatology. 2011;7(7):455.

Full Article

Basseri RJ et al. Intestinal methane production in obese individuals is associated with a higher body mass index. Gastroenterology & Hepatology. 2012;8(1):22.

Full Article

Abstracts, Posters and Presentations

Wacher V et al. Pharmacokinetics of SYN-010 modified-release lovastatin lactone in healthy volunteers:

methane-reducing drug levels are delivered to the colon at doses that alleviated symptoms of irritable bowel syndrome with constipation (IBS-C) in Phase 2a clinical trials. JDDW 2017

Poster

Gottlieb K et al. Increased pulmonary CO2 excretion in patients with small intestinal bacterial overgrowth (SIBO): Possible implications for COPD. DDW 2017

Poster

Le C et al. Initial paradoxical peaks on breath testing (first sample high) do not affect the diagnostic utility of the spot-methane breath test. DDW 2017

Poster

Gottlieb et al. Initial Paradoxical Peaks on Breath Testing (first sample high) do not Affect the Diagnostic Utility of the Spot-methane Breath Test. DDW 2017

Poster

Gottlieb K et al. Increased pulmonary CO2 Excretion in Patients with Small Intestinal Bacterial Overgrowth (SIBO): Possible Implications for COPD. DD 2017

Poster

Wacher V, et al. SYN-010, a Proprietary Modified-Release Formulation of Lovastatin Lactone, Lowered Breath Methane and Improved Stool Frequency in Patients with IBS-C. APDW 2016

POSTER

Wacher V, et al. SYN-010 Modified-Release Lovastatin Does Not Significantly Alter Lipid Parameters at Doses that Reduce Methane and Alleviate Symptoms in Patients Suffering Irritable Bowel Syndrome with Constipation (IBS-C). ACG 2016

Poster

Gottlieb K, et al. Accurate Identification of Excessive Methane Gas Producers Is Possible by a Single Fasting Measurement of Methane. ACG 2016.

POSTER

Gottlieb K, et al. SYN-010, a Proprietary Modified-Release Formulation of Lovastatin Lactone, may Improve Constipation by Inhibiting Enzymes in the Archaeal Methanogenesis Pathway: Results of Computational M. smithii Enzyme-Ligand Docking Experiments. DDW 2016.

Poster

Gottlieb K, et al. SYN-010, a Proprietary Modified-Release Formulation of Lovastatin Lactone, Lowered Breath Methane and Improved Stool Frequency in Patients with IBS-C: Results of a Multi-Center Randomized Double-Blind Placebo-Controlled Phase 2a Trial. DDW 2016.

Poster

Marsh E et al. Lovastatin Lactone Inhibits Methane Production in Human Stool Homogenates. ACG 2015.

Poster

Morales W et al. Lovastatin improves stool form in Methanobrevibacter smithii colonized rats with constipation. DDW 2015.

Abstract Poster

SYN-005

Treatment of Pertussis (Whooping Cough)

Papers

Nguyen AW et al. PERTUSSIS A cocktail of humanized anti–pertussis toxin antibodies limits disease in murine and baboon models of whooping cough. Science Translational Medicine. 02 Dec 2015: Vol. 7, Issue 316, pp. 316ra195.

Full Article Abstract

Abstracts, Posters and Presentations

Maynard J, et al. Monoclonal Antibody Administration Provides Five Weeks of Pertussis Prophylaxis in Newborn Baboons: PoC for Passive Immunization to Protect Infants in the Developing World. ECCMID 2017

Poster

Vert-Wong E et al. Clinical Development for Monoclonal Antibody Therapy to Treat and Prevent Neonatal Pertussis. WAidid 2016.

Poster

Vert-Wong E et al. Comparative Potency Study with Monoclonal Antibody Therapy in Development for Prevention of Neonatal Pertussis. WAidid 2016.

Poster

Maynard JA et al. Antibody Cocktail Effectively Treats Pertussis in a Baboon Disease Model. ECCMID 2015.

Poster

Kaleko M et al. Spontaneous Identification of Bordetella bronchiseptica in a Baboon Colony: Potential Ramifications for Bordetella pertussis Modeling. ECCMID 2015.

Poster

Kaleko M et al. Rational Design of Antibody Cocktails to Treat Disease Caused by Bordetellae. ICAAC 2014.

Abstract