Infant Bacterial Therapeutics Modifies Ph III Protocol After Meeting with FDA
Following its meeting with the US Food and Drug Administration (FDA) in Washington DC to discuss the design of the company’s clinical development program, IBT has chosen to modify its Phase III study of IBP-9414 for the prevention of necrotizing enterocolitis (NEC) in premature infants. With guidance from the FDA, IBT will improve the protocol which may allow additional claims such as reduction in “feeding intolerance”, that could increase the market potential of the product and the chances of success in the company’s Phase III study.
Because of these changes, the Phase III study protocol will not start in 2018 as previously communicated but is expected to start during the first half of 2019. Preparations for this study, including the production of clinical trial material and the initiation of clinical sites in Europe and the US, continue and are unaffected by this FDA meeting.
IBT is developing drug candidate IBP-9414 to prevent necrotizing enterocolitis (NEC), a devastating and often fatal disease in premature infants. IBP-9414 contains the active substance Lactobacillus reuteri, which is a human bacterial strain naturally present in breast milk. IBT has an additional project in its portfolio, a second rare disease program, IBP-1016, for the treatment of an unmet medical need in gastroschisis, a severe disease in infants. By developing these drugs, IBT has the potential to fulfill unmet needs for diseases where there are currently no prevention or treatment therapies available.
SkinBioTherapeutics Begins Final Phase of Human Studies
SkinBioTherapeutics plc (AIM: SBTX – “SkinBioTherapeutics” or the “Company”) announced on 11/20/18 the commencement of the third and final phases of its human study. The final phase of the study seeks to ensure that the original SkinBiotix technology retains the same beneficial property to improve skin barrier health when in a cream formulation. The Company is pleased to announce that the first of its 120 volunteers commenced testing last week. Provisional results for some of the volunteers are expected to be available for analysis at the end of December with the full read out on all 120 volunteers expected during Q1 2019.
The results of this final phase will complete the data pack the company will share with potential global partners interested in commercializing the SkinBiotix technology in the cosmetic skin care market.
Synlogic Presents Data at the 2018 Liver Meeting, the Annual Meeting of the American Association for the Study of Liver Disease (AASLD)
Synlogic, Inc. (Nasdaq: SYBX), a clinical-stage drug discovery and development company applying synthetic biology to beneficial microbes to develop novel living medicines, today announced the presentation of data from a cross-sectional study on ammonia levels in patients with cirrhosis and healthy volunteers, and preclinical studies of its Synthetic Biotic strains in rodent models of liver failure. The presentations were made at The Liver Meeting, the annual meeting of the American Association for the Study of Liver Disease (AASLD), which is being held in San Francisco, November 9 to 13, 2018.
“Hepatic Encephalopathy is a major cause of morbidity and mortality in patients with chronic liver disease. Elevated blood ammonia is an important risk factor for HE, however, it is difficult to measure in the setting of multicenter clinical trials,” said Aoife Brennan, M.B., Ch. B., Synlogic’s president and chief executive officer “The confirmatory preclinical data presented at this meeting support the ongoing development of SYNB1020. In addition, the data provided by our cross-sectional study have enabled us to maximize the quality of ammonia measurement in our ongoing Phase 1b /2a clinical trial of SYNB1020.”
Two presentations were given at the Liver Meeting, both were selected as posters of distinction. The data are summarized below:
Blood Ammonia Levels are Labile and Responsive to Protein Intake in Patients with Compensated Cirrhosis Without Overt Hepatic Encephalopathy
Synlogic conducted a study in patients with cirrhosis who have not had an episode of overt hepatic encephalopathy (HE) to determine the level and inter-individual variability of fasting blood ammonia and the impact of a standard protein meal on blood ammonia levels. In addition, blood ammonia reference ranges of healthy volunteers at five clinical sites were compared as well as the intra-sample variability between fresh samples or fresh and frozen samples.
The data demonstrated that:
- Sample handling and processing have a major impact on ammonia levels and are critical for data quality
- Venous ammonia is elevated in a subset of patients with cirrhosis without a history of overt HE and increases significantly after a meal containing 20g of protein for at least two hours
- Normal ranges determined using healthy volunteers and strict sample processing and analysis procedures can differ significantly from the normal range provided by the kit manufacturer
- There is an excellent correlation between paired fresh samples, however, freezing affects ammonia levels
- Age and gender do not appear to influence ammonia levels, however, as expected, higher MELD score is associated with higher baseline ammonia
The study provided key foundational data for the establishment of optimal protocols for blood ammonia measurement in Synlogic’s ongoing Phase 1b/2a clinical trial of its ammonia consuming Synthetic Biotic strain, SYNB1020, in patients with cirrhosis and elevated ammonia.
Genetically Engineered E.coli Nissle Attenuates Hyperammonemia in Two Experimental Models of Hepatic Encephalopathy
The study was designed to explore the effect of Synthetic Biotic strains engineered to consume ammonia on plasma ammonia levels and bio-markers of liver damage in two rodent models of liver damage, the mouse thioacetamide (TAA) model and the rat bile duct ligation (BDL) model. The rat BDL model studies were conducted in the laboratory of Synlogic’s collaborator, Christopher Rose, Ph.D., Professor at the Department of Medicine at the Université de Montréal and a researcher at the Centre de recherche du Centre hospitalier de Université de Montréal (CRCHUM) where he heads the Hepato-Neuro Laboratory.
The study evaluated two engineered strains of E.coli Nissle: SYNARG, designed to consume ammonia and convert it to arginine, and SYNARG+BUT which was engineered to also synthesize the short chain fatty acid butyrate in the gastrointestinal (GI) tract. Butyrate has been reported to reduce inflammation and help maintain gut barrier integrity.
The data demonstrated that:
- In vitro SYNARG and SYNARG+BUT both consume ammonia and produce arginine and SYNARG+BUT also produces butyrate
- Statistically significant reductions in serum ammonia were observed in both the mouse TAA and rat BDL models
Markers of liver injury were reduced in TAA mice, suggesting additional potential benefits of the engineered strains in liver disease beyond the direct consumption of ammonia in the GI tract
Future studies will also explore the effect of Synthetic Biotic medicines on measures of cognitive function in the rat BDL model. Elevated levels of ammonia in the brain lead to neurological symptoms, including impaired memory, shortened attention span, seizures, lack of muscle coordination and coma. The study provided supportive evidence for the potential beneficial effect of Synthetic Biotic medicines designed to consume ammonia from the GI tract in attenuating chronic liver disease.