Scientific Publications

SYN-004 (ribaxamase)

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

Papers

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

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. 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

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