SSIs for IBD
“Current treatments for IBD suppress the immune system to treat the symptoms of the disease. At Qu, we’re working to treat the underlying cause of the disease by restoring the body’s normal innate immune response.”
Qu Biologics’ QBECO SSI, an investigational treatment for inflammatory bowel disease (IBD), is derived from components of inactivated E. coli bacteria and is designed to restore the body’s normal innate immune response in the gastrointestinal tract. Rather than suppressing the immune system like current IBD treatments, SSIs are designed to restore normal immune function and clear the underlying trigger for the disease.
Dr. Hal Gunn talks about QBECO SSI investigational treatment for IBD
We have completed enrollment of our Crohn’s disease clinical trial and initial results are now available (see below).
We have had tremendous interest in our ulcerative colitis study and all spots for the first group of participants for this clinical trial have been filled. Enrollment of a second group of participants into this clinical trial is expected to begin later in the year. More information about these clinical trials can be found at www.quibd.com. Plans are underway for follow-on, multi-center clinical trials for Crohn’s disease and ulcerative colitis.
Treating the underlying immune dysfunction in Crohn’s disease and ulcerative colitis
Crohn’s disease and ulcerative colitis are a result of a defective immune response in the gastrointestinal tract, leading to chronic inflammation. There are two important arms of the body’s immune system – the innate immune system and the adaptive immune system. Current treatments for Crohn’s disease and ulcerative colitis suppress the adaptive immune system, but these treatments are not curative, which means that most patients will have the disease and be on treatment for the rest of their lives. And these treatments benefit only a portion of patients and can have serious side effects.
Qu Biologics’ scientific team is exploring the treatment of Crohn’s disease and ulcerative colitis in an entirely different way – by restoring the normal function of the innate immune system to resolve what may be the underlying trigger for these diseases. There is growing evidence that a defect / deficiency / immunosuppression of the innate immune system may underlie IBD. There are several hundred gene abnormalities associated with IBD that increase the risk for these diseases, many of which are associated with reduced innate immune system function and, specifically, reduced ability of the innate immune system to optimally clear bacterial infection1,2. Monocytes and macrophages are important sentinel cells of the innate immune system. The monocytes of people with active Crohn’s disease are unproductively immunosuppressive, resulting in an inability to clear bacterial infection in the gastrointestinal tract, leading to invasion of the mucosal lining of the g.i. tract with multiple pathogenic species3–5. Read more about monocyte and macrophage function in inflammatory bowel disease.
Substantial new data supports the concept that IBD is the result of ongoing chronic infection in the gastrointestinal mucosa with multiple pathogenic bacterial species6,7. The adaptive immune system reacts against this chronic infection, resulting in further inflammation, tissue damage and symptoms, but without the support of a normally functioning innate immune system, the over reactive adaptive immune system is unable to clear the chronic infection. Rather than suppressing the adaptive immune response, which further impairs the normal functioning of the immune system, Qu Biologics’ SSIs are designed to recruit activated immunocompetent macrophages to the gastrointestinal tract, restoring normal innate immune response and clearing the chronic infection. Qu Biologics hypothesizes that once this chronic infection is cleared, the over reactive adaptive immune response and inflammation associated with it may resolve, and sustained remission off all medications may be achievable. The data from the small number of patients treated to date in our compassionate use program suggests that this may be possible in a portion of patients.
Stimulating an innate immune response targeted to the GI tract
Qu Biologics’ SSIs are designed to restore innate immune system function and health in the targeted organ or tissue. Each SSI contains components of inactivated bacteria from a single bacterial species that is a common cause of infection in the targeted organ or tissue, for example, the gastrointestinal tract. QBECO SSI, derived from an inactivated enteropathic (i.e., cause of gastrointestinal infection) strain of E. coli, is designed to treat inflammatory bowel disease by recruiting activated innate immune cells to the gastrointestinal tract and restoring normal immune function.
Clinical trials: Crohn’s disease and ulcerative colitis
Qu Biologics has completed enrollment of a Health Canada approved 68 patient randomized, placebo-controlled clinical trial for the treatment of Crohn’s disease. Based on the Week 8 and preliminary Week 16 results, QBECO SSI appears safe and well-tolerated and demonstrates consistently positive trends throughout the treatment period of the trial, successfully establishing proof-of-concept in Crohn’s disease and supporting continued development of QBECO SSI in inflammatory bowel disease.
Qu Biologics has also begun a Phase 2a trial for the treatment of ulcerative colitis. Three clinical trial sites in Vancouver, Edmonton and Hamilton are taking part. We have had strong interest in this study and all spots for the first group of participants for this clinical trial have been filled. Enrollment of a second group of participants into this clinical trial is expected in early 2017. If you are interested in learning more about this clinical trial, call 1-855-209-9680 or email email@example.com.
Plans are underway to begin a larger, multi-center clinical trial in our lead program in Crohn’s disease. If you are interested in participating in and receiving updates about future clinical trials in Crohn’s disease involving Qu Biologics’ Site Specific Immunomodulators (SSIs), please email firstname.lastname@example.org indicating your request.
Clinical Use of SSIs in Inflammatory Bowel Disease – Clinical and Compassionate Use Programs
Based on Week 8 and preliminary Week 16 results, QBECO SSI appears safe and well-tolerated and demonstrates consistently positive trends throughout the treatment period of the trial, successfully establishing proof-of-concept in Crohn’s disease and supporting continued development of QBECO SSI in inflammatory bowel disease.
From 2010 to 2013, ten patients with moderate to severe Crohn’s disease and two patients with moderate to severe ulcerative colitis were treated with QBECO SSI in a compassionate use program. All patients had active disease that was uncontrolled by standard treatment at time of enrollment. Read about the excellent safety profile and promising clinical data in Qu Biologics’ compassionate use program in Crohn’s disease and ulcerative colitis.
A scientific manuscript reporting Qu’s compassionate use data in Crohn’s disease has been published in Gastroenterology Practice and Research. Read the compassionate results in the journal here.
Preclinical research in inflammatory bowel disease
Qu Biologics continues to conduct preclinical research of QBECO SSI for the treatment of inflammatory bowel disease, both in our own research laboratories and in collaboration with the following academic collaborators:
University of British Columbia’s Dr. Bruce Vallance
Qu is collaborating with Dr. Bruce Vallance at the Child & Family Research Institute at BC Children’s Hospital and the University of British Columbia. Dr. Vallance’s team is studying the therapeutic effects of Qu Biologics’ SSI treatment for inflammatory bowel disease (Crohn’s disease and ulcerative colitis) in a mouse model that mimics the underlying innate immune system defect and chronic bacterial infection associated with these diseases.
University of Rochester School of Medicine’s Dr. Michael Elliott
Qu is collaborating with Dr. Michael R. (Rusty) Elliott, Assistant Professor of Microbiology at the University of Rochester School of Medicine. Dr. Elliott is a recognized expert in macrophage function and cell clearance, and his lab is testing the capacity of SSIs to activate macrophages for enhanced activity in vivo using novel mouse models and state-of-the-art immunologic assays systems.
McMaster University’s Dr. Brian Coombes
Qu Biologics has also collaborated with McMaster University Associate Professor and Canada Research Chair, Dr. Brian Coombes, a microbiology expert, to study the efficacy of QBECO SSI in a new preclinical research model for Crohn’s disease. Dr. Coombes’ recently published work in Nature Communications demonstrated that infection in mice with a strain of Crohn’s associated adherent-invasive pathogenic E. coli leads to the development of intestinal inflammation in the mice which closely resembles human Crohn’s disease.
- Hayee, B., Rahman, F. Z., Sewell, G., Smith, A. M. & Segal, A. W. Crohn’s disease as an immunodeficiency. Expert Rev. Clin. Immunol.6, 585–96 (2010).
- Marks, D. J. B., Rahman, F. Z., Sewell, G. W. & Segal, A. W. Crohn’s disease: an immune deficiency state. Clin. Rev. Allergy Immunol.38, 20–31 (2010).
- Casanova, J.-L. & Abel, L. Revisiting Crohn’s disease as a primary immunodeficiency of macrophages. J. Exp. Med.206, 1839–43 (2009).
- Vavricka, S. R. & Rogler, G. New insights into the pathogenesis of Crohn’s disease: are they relevant for therapeutic options? Swiss Med. Wkly.139, 527–34 (2009).
- Mokry, M. et al. Many inflammatory bowel disease risk loci include regions that regulate gene expression in immune cells and the intestinal epithelium. Gastroenterology146, 1040–7 (2014).
- Marteau, P. & Chaput, U. Bacteria as trigger for chronic gastrointestinal disorders. Dig. Dis.29, 166–71 (2011).
- Hansen, R., Thomson, J. M., El-Omar, E. M. & Hold, G. L. The role of infection in the aetiology of inflammatory bowel disease. J. Gastroenterol.45, 266–76 (2010).