Monthly Archives: June 2014

Synthetic Biologics, Inc. announces Clinical Advisory Board to support Novel C. difficile prevention program

*In The News*

Synthetic Biologics, Inc. a developer of novel anti-infective biologic and drug candidates targeting specific pathogens that cause serious infections and diseases, announced today the formation of a Clinical Advisory Board (CAB) to support development of SYN-004, the Company’s lead anti-infective product candidate for the prevention of the devastating effects of Clostridium difficile (C. difficile). The new CAB is comprised of industry leaders Mark Wilcox, M.D., (Chairman), Curtis Donskey, M.D., Ciarán Kelly, M.D. and Tom Louie, M.D., all of whom will provide expertise and guidance on each aspect of the C. diff clinical program.

SYN-004 has the potential to protect the gut microbiome from the effects of IV beta-lactam antibiotics for the prevention of C. difficile infection. Synthetic Biologics expects to initiate Phase Ia and Ib clinical trials to evaluate SYN-004 in the second half of 2014, with preliminary topline data expected by year-end 2014. A Phase II efficacy study of SYN-004 is expected to begin in the first half of 2015.

“As we move closer to initiating human clinical trials of SYN-004, and build our global leadership position in the C. difficile prevention space, we are pleased to assemble this group of highly experienced and knowledgeable advisors to guide clinical development of our program,” stated Jeffrey Riley,CEO of Synthetic Biologics. “Synthetic Biologics’ new CAB combines some of the strongest collective expertise in the C. difficile area, and we should benefit greatly from its insight and guidance as we move toward the clinic.”

“I’m pleased to chair Synthetic Biologics’ C. difficile CAB,” said Dr. Wilcox. “SYN-004 has the potential to have a significant impact on mitigating this urgent public health threat, and I look forward to working with the other advisory board members to help the Company move this promising program forward as expeditiously and strategically as possible.”

Professor Mark Wilcox M.D., FRCPath, is a Consultant Microbiologist, Head of Microbiology and Academic Lead of Pathology at the Leeds Teaching Hospitals (LTHT), Professor of Medical Microbiology at the University of Leeds at their Institute of Biomedical and Clinical Sciences, and is the lead on Clostridium difficile for Public Health England in the UK. He was formerly the Director of Infection Prevention, Infection Control Doctor and Clinical Director of Pathology at LTHT. Dr. Wilcox is deputy Chair of the UK Department of Health’s Antimicrobial Resistance and Healthcare Associated Infection Committee and is a member of the HPA’s Program Board on Healthcare Associated Infection & Antimicrobial Resistance. He has a track record of translational research, including providing the basis of clinical advice to the NHS. He has been the Principal/UK Investigator for several clinical trials of new anti-infective drugs and has provided clinical advice as part of the FDA/EMA submissions for the approval of several novel antimicrobial agents.

Curtis Donskey, M.D., is Associate Professor of Medicine at Case Western Reserve University School of Medicine, as well as Chairman of the Infection Control Committee at the Louis Stokes Cleveland Veterans’ Affairs Medical Center. His expertise and research focus includes the epidemiology and transmission of C. difficile infections in the elderly and in nursing home populations, as well as the infection control issues of antibiotic use. Dr. Donskey has moderated a number of national conferences on the epidemiology of C. difficile.

Ciarán P. Kelly, M.D., is Professor of medicine at Harvard Medical School, as well as Director of Gastroenterology Fellowship Training and Medical Director of the Celiac Center at Beth Israel Deaconess Medical Center in Boston, MA. Dr. Kelly has longstanding clinical and research interests into the causes, diagnosis and treatment of Clostridium difficile infection, and he leads NIH-funded research on C. difficile colitis. Dr. Kelly has authored numerous clinical and basic research book chapters, invited reviews, and more than 100 peer-reviewed publications appearing in such journals as Infection & Immunity, American Journal of Physiology, Gastroenterology, Journal of Biological Chemistry, Journal of Clinical Investigation, The Lancet and New England Journal of Medicine.

Thomas Louie, M.D., is Professor of Medicine in the department of medicine and microbiology-immunology & infectious diseases at the University of Calgary in Alberta, Canada. He also serves as Infection Prevention & Control officer at Alberta Health Services, and was the Medical Director of the infection prevention and control program in the Calgary Health Region 1998-2013. He is involved in clinical trials of new antimicrobial agents primarily for the treatment of C. difficile infection. His research interests include the ecology of hospital-acquired infections in patients receiving antibiotics, and studies on the role of the gut microflora and its replacement by fecal transplantation for the treatment of recurrent C. difficile infection, and possible roles for the prevention of other nosocomial infections.

About Synthetic Biologics, Inc.

Synthetic Biologics, Inc. is a biotechnology company focused on the development of novel anti-infective biologic and drug candidates targeting specific pathogens that cause serious infections and diseases. The Company is developing an oral biologic to protect the gastrointestinal microflora from the effects of IV antibiotics for the prevention of Clostridium difficile infection, an oral treatment to reduce the impact of methane producing organisms on constipation-predominant irritable bowel syndrome (C-IBS), a series of monoclonal antibodies for the treatment of Pertussis and Acinetobacter infections, and a biologic targeted at the prevention and treatment of a root cause of a subset of IBS. In addition, the Company is developing an oral estriol drug for the treatment of relapsing-remitting multiple sclerosis (MS) and cognitive dysfunction in MS. For more information, please visit Synthetic Biologics’ website at www.syntheticbiologics.com.

This release includes forward-looking statements on Synthetic Biologics’ current expectations and projections about future events. 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. These statements are based upon current beliefs, expectations and assumptions and are subject to a number of risks and uncertainties, many of which are difficult to predict and include statements regarding the expected contribution of the CAB members, the potential for SYN -004 and the timing of the clinical trials. The forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those set forth or implied by any forward-looking statements. Important factors that could cause actual results to differ materially from those reflected in Synthetic Biologics’ forward-looking statements include, among others, our failure to initiate trials within the anticipated time frame, the ability to successfully integrate the clinical advisory board members and other factors described in Synthetic Biologics’ report on Form 10-K for the year ended December 31, 2013 and any other filings with the SEC. 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.

SOURCE Synthetic Biologics, Inc.

http://www.streetinsider.com/Press+Releases/Synthetic+Biologics+Forms+Clinical+Advisory+Board+to+Support+Novel+C.+difficile+Preventative+Program/9622506.html

 

Fecal Microbiota Transplant - Study Provides Insight Into Structural/Metabolic Changes That Occur After FMT

cdiffFMTimage

Fecal microbiota transplantation

The process of delivering stool bacteria from a healthy donor to a patient suffering from intestinal infection with the bacterium Clostridium difficile works by restoring healthy bacteria and functioning to the recipient’s gut, according to a study published this week in mBio®, the online open-access journal of the American Society for Microbiology.

The study provides insight into the structural and potential metabolic changes that occur following fecal transplant, says senior author Vincent B. Young, MD, PhD, an associate professor in the Department of Internal Medicine/Infectious Diseases and the Department of Microbiology & Immunology at the University of Michigan in Ann Arbor. The transplants, which have been successful at curing more than 90 percent of recipients, have been used successfully since the 1950s, he says, though it hasn’t been clear how they work to recover gut function.

“The bottom line is fecal transplants work, and not by just supplying a missing bug but a missing function being carried out by multiple organisms in the transplanted feces,” Young says. “By restoring this function, C. difficile isn’t allowed to grow unchecked, and the whole ecosystem is able to recover.”

Young and colleagues used DNA sequencing to study the composition and structure of fecal microbiota (bacteria) in stool samples from 14 patients before and two to four weeks after fecal transplant. In 10 of the patients, researchers also compared stool samples before and after transplant to samples from their donors.

All transplant patients, treated at the Essentia Health Duluth Clinic in Minnesota, had a history of at least two recurrent C. difficile infections following an initial infection and failed antibiotic therapy.

Studying families of bacteria in the samples, investigators found marked differences among donor, pre-transplant and post-transplant samples. However, those from the donors and post-transplant patients were most similar to each other, indicating that the transplants at least partially returned a diverse community of healthy gut bacteria to the recipients. While not as robust as their donors, the bacterial communities in patients after transplant showed a reduced amount of Proteobacteria, which include a variety of infectious agents, and an increased amount of Firmicutes and Bacteroidetes bacteria typically found in healthy individuals, compared to their pre-transplant status.

Then, using a predictive software tool, researchers analyzed the relationship between the community structure of the micoorganisms and their function, presumably involved in maintaining resistance against CDI.

They identified 75 metabolic/functional pathways prevalent in the samples. The samples taken from patients before transplant had decreased levels of several modules related to basic metabolism and production of chemicals like amino acids and carbohydrates, but were enriched in pathways associated with stress response, compared to donor samples or post-transplant samples.

CDI has significantly increased during the past decade, Young says, with previous studies estimating there are more than 500,000 cases of CDI in the United States annually, with health care costs ranging from $1.3 billion to $3.4 billion. Up to 40 percent of patients suffer from recurrence of disease following standard antibiotic treatment. In a healthy person, gut microorganisms limit infections but antibiotics are believed to disrupt the normal structure of these microoganisms, rendering the gut less able to prevent infection with C. difficile.

Further identification of the specific microorganisms and functions that promote resistance of bacterial colonization, or growth, may aid in the development of improved CDI treatments, Young says: “If we can understand the functions that are missing, we can identify supplemental bacteria or chemicals that could be given therapeutically to help restore proper gut function.”

For article in its entirety click on the link below:

http://www.eurekalert.org/pub_releases/2014-06/asfm-ftr061214.php

 

The study was supported by the National Institutes of Health, the Michigan Gastrointestinal Peptide Research Center, and the Essentia Health Foundation in Duluth, Minn.

mBio® is an open access online journal published by the American Society for Microbiology to make microbiology research broadly accessible. The focus of the journal is on rapid publication of cutting-edge research spanning the entire spectrum of microbiology and related fields. It can be found online at http://mbio.asm.org.

The American Society for Microbiology is the largest single life science society, composed of over 39,000 scientists and health professionals. ASM’s mission is to advance the microbiological sciences as a vehicle for understanding life processes and to apply and communicate this knowledge for the improvement of health and environmental and economic well-being worldwide.

 

Clostridium difficile Research and Development May/June 2014

laboratorybeakers3

 

Here’s the latest from the

Clostridium difficile research community:
Formaldehyde, a chemical commonly used to inactivate bacterial products, plays an important role in the formulation of a toxoid vaccine against C. difficile infection. In this paper, B. Wang describes how the toxicity of Toxin B (TcdB) can be removed by a treatment with formaldehyde solution but states that the storage of the formaldehyde-treated toxin can result in a reversion of the detoxification treatment, reestablishing toxicity. The authors highlight the importance of maintaining a minute amount of formaldehyde in liquid formulations, which prevents the reversion to toxicity.
http://www.ncbi.nlm.nih.gov/pubmed/24951860
One of the most successful treatments for Clostridium difficile infection is a fecal microbiota transplant (FMT), in which a patient’s intestinal microbiome is reestablished using the stool from another individual. Here, the authors evaluate the changes in fecal microbiota structure post-fecal transplantation using metagenomic sequencing of the 16S rRNA. It was found that a patient’s intestinal microbiota was more diverse, with a lower number of Proteobacteria but a higher number of Bacteriodetes, along with functional changes in the overall microbial structure as compared to pre-FMT.
http://www.ncbi.nlm.nih.gov/pubmed/24939885
A patient’s risk to Clostridium difficile infection can be determined by analyzing antibody levels to Toxin A (TcdA). In contrast to the accepted belief that TcdA is the key virulence factor in CDI, J. Islam evaluated the role of TcdA and TcdB antibodies in patients to determine their susceptibility to infection and found that mucosal immunity to TcdB can be a significant factor in determining early stages of infection, a target for preventing its advancement.
http://www.ncbi.nlm.nih.gov/pubmed/24708941
Clostridium difficile spores are the leading culprits in the spread of CDI because they can survive in the environment for long periods of time and are resistant to most cleaning products. Here, an outbreak of Clostridium difficile infection is reported in a hospital and is linked to the contamination of mop pads after a laundry machine mishap.
http://www.ncbi.nlm.nih.gov/pubmed/24837118

 

Chandrabali Ghose-Paul,MS,PhD, Chairperson of Research and Development

Synthetic Biologics, Inc. and Enterome Bioscience SA enter into researching effects of beta-lactam antibiotics on the Microbiome

NewsSpeaker

 

Synthetic Biologics, Inc. (NYSE MKT: SYN), a developer of novel anti-infective biologic and drug candidates targeting specific pathogens that cause serious infections and diseases, and Enterome Bioscience SA, a pioneer in the development of innovative disease management solutions based on a deep understanding of the gut microbiome, today announced that they have entered into an agreement to conduct metagenomic research on the effects of beta-lactam antibiotics on the gastrointestinal microflora (microbiome) of human patients. As part of this collaboration, a clinical microbiome study of approximately 100 patients is expected to begin next month. Research findings should provide important insights as Synthetic Biologics advances the development of SYN-004, which is intended to protect the gut microbiome from the effects of intravenous (IV) beta-lactam antibiotics, and in particular to prevent C. difficile (C. diff) infections. Phase Ia and Ib clinical trials of Synthetic Biologics’ SYN-004 are scheduled to begin later this year.

The Enterome microbiome study, scheduled for completion in the second half of 2014, is expected to provide a better understanding of the harmful effects of beta-lactam antibiotics on the gut bacterial community. The goal is to establish a “fingerprint” of the damage caused by beta-lactam antibiotics, thus yielding a panel of bacterial biomarkers that can be leveraged for diagnostic purposes. This novel study should clearly define the impact of beta-lactam antibiotics on the natural bacterial diversity of the gut microbiome. Changes in the gut microbiome have been related to multiple diseases, including C. diff infections, antibiotic-associated diarrhea, obesity, diabetes and other metabolic diseases. This study will utilize Enterome’s state-of-the-art shotgun metagenomic sequencing technology to profile the human gut microbiome.

“We are pleased to establish this collaboration with Enterome, a pioneer in the development of biomarkers and therapies for diseases of the gut microbiome,” stated Jeffrey Riley, CEO of Synthetic Biologics. “Findings from this study should support our C. diff therapeutic program, which focuses on protecting and maintaining the balance of bacterial microflora in the gut, while also establishing our presence in Europe.”

Synthetic Biologics’ lead anti-infective product candidate, SYN-004, is the first therapy designed to neutralize IV antibiotics in the gut, and is intended to protect and maintain the balance of bacterial flora in the gastrointestinal tract, to prevent the devastating effects of C. diff. The U.S. Centers for Disease Control and Prevention (CDC) has classified C. diff as an “urgent public health threat”i, surpassing Methicillin-resistant Staphylococcus aureus (MRSA) as the number one hospital-acquired infection in the United States. C. diff is a multidrug-resistant bacterium that infects 1.1 million U.S. patients annuallyii. In the U.S., patients with C. diff are hospitalized an estimated 3.6-7 extra daysiii, costing more than $8.2 billioniv.

“The signing of this agreement with Synthetic Biologics is another important corporate milestone for Enterome. I am very pleased that our pioneering approach to understanding the linkage between changes in the gut microbiome and disease has convinced Synthetic Biologics to work with us on such an important personalized medicine project. It is clear that new diagnostic solutions are needed to properly address the growing problem of antibiotic-induced dysbiosis and associated hospital-acquired bacterial infections,” stated Pierre Belichard, CEO of Enterome. “Tailoring the use of anti-infective treatments based on microbiome profiling is beginning to show great promise as a way to address the management of infectious diseases.”

“Comparing Enterome’s technology to other genomic analyses of gut microbiome is like comparing a Quad Full High definition color resolution TV to resolution of an analog black & white TV,” added Mr. Riley.

About SYN-004 Clinical Development

Synthetic Biologics is developing SYN-004, a novel second generation oral enzyme drug candidate, to be co-administered with commonly used IV beta-lactam antibiotics and is intended to protect the gastrointestinal microflora (microbiome) from the harmful effects of such antibiotics, thus potentially preventing C. diff infections. Planned next steps for SYN-004 include: 1) initiation of a 28-day bridging toxicology study in June 2014; 2) filing of an Investigational New Drug (IND) application to initiate Phase Ia and Ib clinical trials in the second half of 2014, with preliminary topline data expected by year-end 2014; and, 3) initiation of a Phase II efficacy study is expected to begin in the first half of 2015.

About Enterome Bioscience SA

Enterome is pioneering the development of innovative disease management solutions based on a deep understanding of the gut microbiome. Understanding and modifying the changes that occur in the gut microbiome during disease and in response to therapeutic interventions represent an entirely new and untapped opportunity to impact medicine.

Initially Enterome is using its expertise and proprietary technologies to develop novel diagnostic products to support patient stratification, personalized therapies and the clinical development of new drugs for the treatment of microbiome-related diseases such as inflammatory bowel diseases and metabolic diseases (diabetes and obesity). Enterome’s unique Metagenotyping® process has allowed it to develop biomarkers for treatment response prediction, disease activity monitoring and as potential companion diagnostics.

The company was established in 2012 in Paris, France, and has raised a total of €17.5m from leading venture capital investors (Seventure, Omnes Capital & Lundbeckfond Ventures) and two strategic investors (Danone & Shire). www.enterome.com

About Synthetic Biologics, Inc.

Synthetic Biologics, Inc. (NYSE MKT: SYN) is a biotechnology company focused on the development of novel anti-infective biologic and drug candidates targeting specific pathogens that cause serious infections and diseases. The Company is developing an oral biologic to protect the gastrointestinal microflora from the effects of IV antibiotics for the prevention of Clostridium difficile (C. difficile) infection, an oral treatment to reduce the impact of methane producing organisms on constipation-predominant irritable bowel syndrome (C-IBS), a series of monoclonal antibodies for the treatment of Pertussis and Acinetobacter infections, and a biologic targeted at the prevention and treatment of a root cause of a subset of IBS. In addition, the Company is developing an oral estriol drug for the treatment of relapsing-remitting multiple sclerosis (MS) and cognitive dysfunction in MS. For more information, please visit Synthetic Biologics’ website at www.syntheticbiologics.com.

 

* For article in its entirety please click on the following link:

http://www.prnewswire.com/news-releases/synthetic-biologics-and-enterome-bioscience-collaborate-on-microbiome-research-to-support-synthetic-biologics-c-difficile-program-262479001.html

Raising C Diff Awareness CHICAGO November 4, 2014

CONFERENCE

#RCDAChicago

Join us at the second annual

“Raising C Diff Awareness” Conference

 

 

The C Diff Foundation is proud to host this conference at

the University of Illinois at Chicago - Chicago, IL, USA on November 4th, 2014

Registration is OPEN. Click on the link below to view conference details, guest speakers confirmed to date, while taking advantage of the early-bird registration savings in effect before August 16th.

http://events.r20.constantcontact.com/register/event?oeidk=a07e9h6shhd46356532&llr=6iomnjnab

 

Meridien Research in Tampa Bay - Florida, Seeking Volunteers For C. diff. Vaccine Clinical Research Trial

Sanofi Pasteur MeridienH-030-014_CDIF10010A-1_ STP

Are You at Risk for C. Diff?

C. diff is a bacterium that can cause mild diarrhea to life-threatening bowel disease. The risk of acquiring C. diff. increases with age, the use of antibiotics and time spent in hospitals or in nursing homes.

Volunteers are needed for research study being conducted to evaluate the effects of an investigational vaccine for C.diff infections. You may qualify if you are 50 years old or older, are planning a hospitalization, and/or have had at least 2 recent hospital stays within the past year.

Qualified participants may receive at no cost study-related:
● Evaluations, physical exams, routine lab work
 ● Investigational medication or placebo

Compensation for time and travel may be available. No medical insurance is necessary.

Call 1-727-347-8839 (USA) for more information.

About Meridien

Meridien Research provides patients and families in the Tampa Bay area an opportunity to take part in clinical research trials for a wide variety of medical conditions. These research trials are usually offered at University or large research institutions, but with offices in Tampa, St. Petersburg, Brooksville, Bradenton and Lakeland, area residents can have access to the latest in medical research without leaving home.

Stephanie Jones, Director of Marketing

Insearch Group

9455 Koger Blvd.

Suite 111

St. Petersburg, FL 33702

727.544.4842

sjones@insearchgroup.net

www.newstudyinfo.com

 

Study Shows the importance of Gut Microbiota in Stem Cell Transplant Outcome

In The News 17 June 2014

New research published online today in Blood, the Journal of the American Society of Hematology (ASH), suggests that the diversity of bacteria in the gastrointestinal tract of patients receiving stem cell transplants may be an important predictor of their post-transplant survival.

A healthy gastrointestinal tract contains a balanced community of microorganisms (known as microbiota), largely comprised of “friendly” bacteria that aid digestion and are important to immune system function. When this community of microbes is compromised, the microbiota may become less diverse, and the body becomes more susceptible to certain diseases.

Previous studies have shown that the intensive treatment given to individuals receiving a stem cell transplant from a healthy donor (known as an allogeneic stem cell transplant or SCT) can destroy a significant portion of the recipients’ gut microbiota and reduce its overall diversity. Disturbances of the gut microbiota have been shown to be correlated with post-transplant complications such as bloodstream infections and graft-versus-host disease.

“While the link between gut microbiota and complications in allogeneic SCT has been previously established, until this point it has remained unclear whether the gut bacteria of transplant recipients could predict their survival,” said senior study author Ying Taur, MD, MPH, of the Lucille Castori Center for Microbes, Inflammation, and Cancer at Memorial Sloan Kettering Cancer Center. “This study sought to further explore the potential connection between transplantation, gut bacteria, and overall survival.”

To better understand the association between post-transplant microbiota and patient outcomes, Dr. Taur and a team of researchers collected fecal specimens from 80 patients undergoing allogeneic SCT and sequenced each sample’s bacterial DNA. Specimens were collected within seven days of engraftment, the point at which transplanted blood-forming cells start to grow and make healthy cells in the recipient and the point at which researchers speculated that microbiota diversity would be greatest following pre-transplant conditioning.

Researchers compared patient outcomes based on diversity of microbiota in their specimens, grouping subjects into high, intermediate, and low microbiota diversity categories. At time of stem cell engraftment, 34 patients (42.5%) were observed to have low gut microbiota diversity, 20 (25%) of patients had intermediate diversity, and 26 (32.5%) patients had high diversity. The analysis continued for up to three years or until death or last follow-up.

Following their analyses, researchers found a strong connection between post-transplant gut microbiota diversity and outcomes, observing overall survival rates of 36 percent, 60 percent, and 67 percent among the low, intermediate, and high diversity groups, respectively. Furthermore, researchers observed that diversity was particularly associated with transplant-related outcomes, concluding that patients with low microbiota diversity were approximately five times more likely to die of transplant-related causes within the follow-up period than those with more diverse gut bacteria.

“These results further underscore the significance of the gut microbiota in allogeneic stem cell transplant. A major question is whether we can improve outcomes by preserving diversity within the gut microbiota,” said Dr. Taur. “One possible strategy is to find ways to perform transplants in a manner that minimizes damage to the gut microbiota. Another approach would be to replenish the gut with beneficial microbes that are lost after this procedure is performed. We hope that this study will inspire additional research that will further examine the role and importance of the gut microbiota to stem cell transplant outcome.”

Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field of hematology, is available weekly in print and online. Blood is the official journal of the American Society of Hematology (ASH) (www.hematology.org), the world’s largest professional society concerned with the causes and treatment of blood disorders.

ASH’s mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems by promoting research, clinical care, education, training, and advocacy in hematology.

blood® is a registered trademark of the American Society of Hematology.

SOURCE American Society of Hematology

and for full article:

http://news.yahoo.com/gut-bacteria-predict-survival-stem-cell-transplant-study-140000698.html?soc_src=copy