David
Co-Founder
Crohnsforum.com was lucky and managed to (virtually) sit down and have an interview with Dr. Hal Gunn, the founding CEO of Qu Biologics. Qu Biologics is a Canadian company developing an exciting potential treatment for Crohn's disease called, "Site Specific Immunomodulation" (SSI).
David Chapman: Dr. Gunn, can you please tell us a little about yourself, your medical training, how long you've been a doctor, and areas of practice/research?
Dr. Gunn: I’ve always been interested in health and supporting the body’s own capacity to heal. I graduated from University of British Columbia medical school 30 years ago and, 15 years ago, co-founded InspireHealth, Canada’s leading integrative medical centre, which we founded to help integrate the concepts of health and immune system support into the treatment of disease. InspireHealth, a not-for-profit, has been funded by the BC government to expand across the province to provide integrative care to British Columbians diagnosed with cancer. My primary interest in practice/research is understanding how to optimally support the body’s own capacity for health and healing.
David Chapman: Please tell us what SSIs are, how SSIs were developed and why you are now looking to treat Crohn's Disease with them.
Dr. Gunn: A large body of research across a number of disease areas shows that the more acute infections you get, the less your risk of cancer and autoimmune diseases such as Crohn’s disease and ulcerative colitis. Acute infection stimulates the body’s innate immune system. There is growing evidence that a defect or deficiency of the innate immune system may be an important underlying cause of both cancer and autoimmune diseases such as Crohn’s disease. We’re developing drugs with the potential to simulate acute infection without actually causing infection, using Site Specific Immunomodulators (SSIs), which appear to stimulate innate immune system function in the targeted organ or tissue, for example, the gastrointestinal tract.
David Chapman: How many patients with Crohn's Disease have been treated with SSIs and how are they doing?
Dr. Gunn: We treated 10 patients with moderate to severe Crohn’s disease in a small clinical study. All 10 patients showed improvement in symptoms and 7 of the 10 patients had clinical remission of their disease. 4 of the 10 patients have had sustained clinical remission and are off all medications, including SSI therapy. The longest sustained remission is 2.5 years. This is a small study and wasn’t a randomized controlled trial, so we can’t make any definitive conclusions. We will soon be starting a larger randomized controlled trial with our investigational treatment to assess the benefits and risks of SSI therapy for Crohn’s disease.
David Chapman: What side effects have patients experienced thus far with SSIs?
Dr. Gunn: We have treated more than 270 patients with cancer and 15 patients with autoimmune disease (including 10 patients with Crohn’s disease) through compassionate use (‘Named Patient Use’) programs and small clinical studies. To date, the safety profile has been very good and the drug has been well tolerated, however, as this is an investigational drug, the full safety profile has not yet been established.. A few patients have had transient fever, likely as a result of stimulation of the immune system, lasting 6 – 24 hours, which resolved with ongoing treatment.
David Chapman: For the doctors and researchers out there, can you explain the science behind how you think SSIs work?
Dr. Gunn: Macrophages are important cells of the body’s innate immune system. One of their primary roles is to engulf (through phagocytosis) dying or dead cells, in order to clear/recycle these dead and dying cells. The cells of the tissues in our body have a natural life cycle, measured in days, weeks or months depending on the tissue. When a cell reaches the end of its natural life cycle, it signals to macrophages that it is dying, a process called apoptosis, inviting macrophages to engulf and recycle the cell. When this happens, the macrophage engulfs the cell and sends out anti-inflammatory and ‘tolerance’ signals so that the adaptive immune system (the other major arm of the immune system) doesn’t react against the antigens of the dying cell.
However, if there is a defect or deficiency of macrophage function (i.e., innate immune system), especially if there is an environmental trigger such as stress or chronic infection that overwhelms macrophage function, macrophages don’t clear dying or dead cells efficiently. As a result, not all dying or dead cells are cleared by macrophages and, when they aren’t cleared, these dead cells necrose (i.e., break apart) releasing their internal antigens to which the adaptive immune system reacts, resulting in antibodies against these self-antigens and autoimmune disease (such as Crohn’s disease). In other words, while symptoms of autoimmune disease are generally understood to be a result of an over-reactive adaptive immune system response, we hypothesize that the underlying trigger/cause may be a defect or deficiency in the innate immune system (macrophage function).
Based on our preclinical research, we’ve found that SSI treatment results in recruitment of macrophages to the targeted organ or tissue (for example, the gastrointestinal tract) with stimulation of their phagocytosis function, which we believe relieves the defect or deficiency that may underlie Crohn’s disease. SSIs are made from killed bacterial components. Injected subcutaneously (i.e., just under the skin), we’ve shown that SSIs stimulate an innate immune response in the organ or tissue in which the bacteria commonly causes infection. An SSI made from E. coli stimulates an innate immune response in the gastrointestinal tract and thus, we are using an E. coli derived SSI in our Crohn’s disease clinical trials.
David Chapman: When should SSIs enter phase I/II clinical trials and who will be eligible?
Dr. Gunn: Our 60 patients phase I/II randomized trial is planned to begin in January or February. Patients with active moderate/severe Crohn’s disease will be eligible for the trial. Half the study patients will be randomized to SSI treatment in addition to their usual treatment, the other half to placebo in addition to their usual treatment. After 8 weeks of treatment, all patients who have not responded to treatment will begin SSI treatment for 8 weeks, so patients who are initially on placebo treatment will have the opportunity to be on SSI treatment. The trial will be conducted in Vancouver, Canada. Patients can fly in to start treatment for the trial and continue treatment at home, returning to Vancouver for reassessment twice as the trial progresses. Initially, Canadian patients will be eligible for the study. We may expand the study to American and international patients if the necessary measures for treating foreign patients in Canada can be put in place.
David Chapman: If someone with Crohn's Disease is interested in the upcoming trial, what should they do?
Dr. Gunn: We welcome patients interested in our upcoming trial, especially Canadian patients, to visit our trial website www.qucrohnstrial.com, which will be launched shortly. The website will provide information about the trial and eligibility criteria. Patients will be able to answer a questionnaire on the site to assess their eligibility for the trial.
David Chapman: If you have good results with the trial, what happens after that?
Dr. Gunn: If our upcoming trial is successful, we will initiate a larger multi-centre trial to further study the efficacy and safety of the treatment in Crohn’s disease and as a further step towards drug approval.
David Chapman: Do you have any parting words for the members of Crohnsforum.com?
Dr. Gunn: I’ve had a long-time interest in patient advocacy and empowerment. I applaud the work of David and all the patients and family members at Crohnsforum.com for everything that you are doing to empower, educate and engage people with Crohn’s disease and am grateful for the opportunity to inform the membership about SSI treatment and our upcoming trial. Thanks so much.
** Added 02/27/2013 - A new video interview with Dr. Gunn:
[youtube]JC6U83EgYAI[/youtube]
*** Added 05/31/2013 - See videos of Crohn's patients who have already taken SSI: http://www.crohnsforum.com/showpost.php?p=657979&postcount=59
David Chapman: Dr. Gunn, can you please tell us a little about yourself, your medical training, how long you've been a doctor, and areas of practice/research?
Dr. Gunn: I’ve always been interested in health and supporting the body’s own capacity to heal. I graduated from University of British Columbia medical school 30 years ago and, 15 years ago, co-founded InspireHealth, Canada’s leading integrative medical centre, which we founded to help integrate the concepts of health and immune system support into the treatment of disease. InspireHealth, a not-for-profit, has been funded by the BC government to expand across the province to provide integrative care to British Columbians diagnosed with cancer. My primary interest in practice/research is understanding how to optimally support the body’s own capacity for health and healing.
David Chapman: Please tell us what SSIs are, how SSIs were developed and why you are now looking to treat Crohn's Disease with them.
Dr. Gunn: A large body of research across a number of disease areas shows that the more acute infections you get, the less your risk of cancer and autoimmune diseases such as Crohn’s disease and ulcerative colitis. Acute infection stimulates the body’s innate immune system. There is growing evidence that a defect or deficiency of the innate immune system may be an important underlying cause of both cancer and autoimmune diseases such as Crohn’s disease. We’re developing drugs with the potential to simulate acute infection without actually causing infection, using Site Specific Immunomodulators (SSIs), which appear to stimulate innate immune system function in the targeted organ or tissue, for example, the gastrointestinal tract.
David Chapman: How many patients with Crohn's Disease have been treated with SSIs and how are they doing?
Dr. Gunn: We treated 10 patients with moderate to severe Crohn’s disease in a small clinical study. All 10 patients showed improvement in symptoms and 7 of the 10 patients had clinical remission of their disease. 4 of the 10 patients have had sustained clinical remission and are off all medications, including SSI therapy. The longest sustained remission is 2.5 years. This is a small study and wasn’t a randomized controlled trial, so we can’t make any definitive conclusions. We will soon be starting a larger randomized controlled trial with our investigational treatment to assess the benefits and risks of SSI therapy for Crohn’s disease.
David Chapman: What side effects have patients experienced thus far with SSIs?
Dr. Gunn: We have treated more than 270 patients with cancer and 15 patients with autoimmune disease (including 10 patients with Crohn’s disease) through compassionate use (‘Named Patient Use’) programs and small clinical studies. To date, the safety profile has been very good and the drug has been well tolerated, however, as this is an investigational drug, the full safety profile has not yet been established.. A few patients have had transient fever, likely as a result of stimulation of the immune system, lasting 6 – 24 hours, which resolved with ongoing treatment.
David Chapman: For the doctors and researchers out there, can you explain the science behind how you think SSIs work?
Dr. Gunn: Macrophages are important cells of the body’s innate immune system. One of their primary roles is to engulf (through phagocytosis) dying or dead cells, in order to clear/recycle these dead and dying cells. The cells of the tissues in our body have a natural life cycle, measured in days, weeks or months depending on the tissue. When a cell reaches the end of its natural life cycle, it signals to macrophages that it is dying, a process called apoptosis, inviting macrophages to engulf and recycle the cell. When this happens, the macrophage engulfs the cell and sends out anti-inflammatory and ‘tolerance’ signals so that the adaptive immune system (the other major arm of the immune system) doesn’t react against the antigens of the dying cell.
However, if there is a defect or deficiency of macrophage function (i.e., innate immune system), especially if there is an environmental trigger such as stress or chronic infection that overwhelms macrophage function, macrophages don’t clear dying or dead cells efficiently. As a result, not all dying or dead cells are cleared by macrophages and, when they aren’t cleared, these dead cells necrose (i.e., break apart) releasing their internal antigens to which the adaptive immune system reacts, resulting in antibodies against these self-antigens and autoimmune disease (such as Crohn’s disease). In other words, while symptoms of autoimmune disease are generally understood to be a result of an over-reactive adaptive immune system response, we hypothesize that the underlying trigger/cause may be a defect or deficiency in the innate immune system (macrophage function).
Based on our preclinical research, we’ve found that SSI treatment results in recruitment of macrophages to the targeted organ or tissue (for example, the gastrointestinal tract) with stimulation of their phagocytosis function, which we believe relieves the defect or deficiency that may underlie Crohn’s disease. SSIs are made from killed bacterial components. Injected subcutaneously (i.e., just under the skin), we’ve shown that SSIs stimulate an innate immune response in the organ or tissue in which the bacteria commonly causes infection. An SSI made from E. coli stimulates an innate immune response in the gastrointestinal tract and thus, we are using an E. coli derived SSI in our Crohn’s disease clinical trials.
David Chapman: When should SSIs enter phase I/II clinical trials and who will be eligible?
Dr. Gunn: Our 60 patients phase I/II randomized trial is planned to begin in January or February. Patients with active moderate/severe Crohn’s disease will be eligible for the trial. Half the study patients will be randomized to SSI treatment in addition to their usual treatment, the other half to placebo in addition to their usual treatment. After 8 weeks of treatment, all patients who have not responded to treatment will begin SSI treatment for 8 weeks, so patients who are initially on placebo treatment will have the opportunity to be on SSI treatment. The trial will be conducted in Vancouver, Canada. Patients can fly in to start treatment for the trial and continue treatment at home, returning to Vancouver for reassessment twice as the trial progresses. Initially, Canadian patients will be eligible for the study. We may expand the study to American and international patients if the necessary measures for treating foreign patients in Canada can be put in place.
David Chapman: If someone with Crohn's Disease is interested in the upcoming trial, what should they do?
Dr. Gunn: We welcome patients interested in our upcoming trial, especially Canadian patients, to visit our trial website www.qucrohnstrial.com, which will be launched shortly. The website will provide information about the trial and eligibility criteria. Patients will be able to answer a questionnaire on the site to assess their eligibility for the trial.
David Chapman: If you have good results with the trial, what happens after that?
Dr. Gunn: If our upcoming trial is successful, we will initiate a larger multi-centre trial to further study the efficacy and safety of the treatment in Crohn’s disease and as a further step towards drug approval.
David Chapman: Do you have any parting words for the members of Crohnsforum.com?
Dr. Gunn: I’ve had a long-time interest in patient advocacy and empowerment. I applaud the work of David and all the patients and family members at Crohnsforum.com for everything that you are doing to empower, educate and engage people with Crohn’s disease and am grateful for the opportunity to inform the membership about SSI treatment and our upcoming trial. Thanks so much.
** Added 02/27/2013 - A new video interview with Dr. Gunn:
[youtube]JC6U83EgYAI[/youtube]
*** Added 05/31/2013 - See videos of Crohn's patients who have already taken SSI: http://www.crohnsforum.com/showpost.php?p=657979&postcount=59
