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Welcome to Celimmune

Celimmune, LLC is a clinical development-stage immunotherapy company dedicated to developing transformational therapies that will relieve the burden of celiac disease and refractory celiac disease (refractory sprue) and other serious immune-mediated diseases.

Celiac Disease

Symptoms of Celiac Disease

Celiac disease causes debilitating symptoms and potentially serious medical complications. Small intestine damage often leads to nutrient malabsorption that can result in a range of further clinical manifestations (anemia, osteopenia/osteoporosis, failure to thrive in children). In addition, extra-intestinal symptoms and systemic manifestations are often present, such as dermatitis, infertility, or neurological and skeletal disorders.

The most serious complication of celiac disease is the development of a gastrointestinal T cell lymphoma after years of exposure to gluten. This malignant condition, which is no longer dependent of gluten or responsive to a gluten-free diet (GFD), is called refractory celiac disease Type II (RCD II), an in situ small bowel T-cell lymphoma.

Green PH, Cellier C. Celiac disease. N Engl J Med 2007; 357:1731-1743.

Malamut G, Cellier C. Refractory celiac disease: epidemiology and clinical manifestations. Dig Dis 2015; 33:221-226.

Lebwohl B, Granath F, Ekbom A, et al. Mucosal healing and risk for lymphoproliferative malignancy in celiac disease: a population-based cohort study. Ann Intern Med 2013; 159:169-175.

Causes of Celiac Disease

Celiac disease is a chronic hereditary systemic autoimmune and inflammatory disease triggered by gluten consumption. In celiac patients, the autoimmune process (the immune system mistakenly attacks and destroys healthy body tissue) starts in the mucosa of the small intestine (the lining of the gut wall), spreading to other organs in approximately one half of patients.

Gluten is a form of protein present in some grains, such as wheat, barley, rye and, to a lesser extent, oats. Gluten is modified by an enzyme called tissue transglutaminase (tTG) and then binds to the immune molecules HLA-DQ2 and HLA-DQ8, triggering an immune reaction against gluten and tTG. The immune reaction to tTG is what separates celiac disease from other diseases that involve gluten. For instance, immune reactivity against gluten but not against healthy body tissue is a different condition called “gluten sensitivity.” Another disease caused by gluten is “wheat allergy”, a food allergy that is also different from the autoimmune celiac disease.

Approximately 1% of the general population has celiac disease. Celiac disease is the most frequent chronic autoimmune gastrointestinal disease, and the prevalence is doubling every 20-30 years.

Green PH, Cellier C. Celiac disease. N Engl J Med 2007; 357:1731-1743.

Schuppan D, Junker Y, Barisani D. Celiac Disease: From pathogenesis to novel therapies. Gastroenterology 2009; 137:1912-1933.

Fasano A, Berti I, Gerarduzzi T, Not T, Colleti RB, Drago S, et al. Prevalence of celiac disease in at risk and not-at-risk groups in the United States: a large multicenter study. Arch Intern Med 2003; 63:286-292.

Riddle MS, Murray JA, Porter CK. The incidence and risk of celiac disease in a healthy US adult population. Am J Gastroenterol 2012; 107:1248-1255.

Diagnosis of Celiac Disease

In many patients, the initial diagnosis is suspected by the presence of gastrointestinal symptoms derived from intestinal mucosal damage or symptoms in other organs with no apparent cause. Blood tests can be done to determine the presence of positive specific blood antibodies (anti-transglutaminase or anti-deamidated gluten peptide antibodies), and a biopsy of the small intestine often reveals intestinal mucosal atrophy, which can confirm a diagnosis of celiac disease.

It should be noted that as many as 1 in 5 celiac patients do not have clearly distinguishable or detectable symptoms and the diagnosis may be difficult to establish in those cases. It is estimated that 83% of Americans who have celiac disease are undiagnosed or misdiagnosed with other conditions.

Green PH, Cellier C. Celiac disease. N Engl J Med 2007; 357:1731-1743.

Celiac Disease

Management: The Gluten-Free Diet

The only currently available management option is a life-long strict adherence to a gluten-free diet (GFD).

A gluten-free diet is a diet that excludes all products containing gluten. In other words, all products made from the flours of wheat, barley, rye and, in many countries (due to frequent cross-contamination), oats.

The main challenge to a total adherence to a gluten-free diet is that grains, or their by-products, are widely used in the food industry and are present in numerous food and household products. Modern diets are increasingly enriched with gluten, which is also used as an additive to processed foods, household items (cosmetics, toothpaste and lipstick) and as an excipient in oral medications. Gluten is the second most common food ingredient after sugar and, in some countries, is present in up to 80% of foodstuff.

Even manufactured “gluten-free” products can contain small amounts of gluten, may be difficult to find, tend to be less flavorful and are more expensive than regular gluten containing products. In addition, labeling of food and household products is deficient in many countries.

Finally, there is no available objective tool for patients to monitor gluten consumption.

For all these reasons, celiac sufferers are regularly exposed to gluten contamination.

The Burden of the Gluten-Free Diet (GFD)

Celiac disease is the only common autoimmune disorder with no approved medication. The only available strategy for the management of celiac disease patients is a lifelong total avoidance of gluten. While simple in theory, the ubiquity of gluten in foodstuffs, medications, household substances, cosmetics, and gluten-free items makes total avoidance of gluten difficult – if not impossible.

As few as 50 milligrams a day (a few bread crumbs) triggers the disease. For comparison, a normal diet contains more than 10 grams per day. Thus, the only currently available management option of a GFD presents both a considerable challenge and substantial burden for patients. A study found the burden of celiac disease and a GFD on patient quality of life was ranked second only to end-stage renal disease – a condition that requires multiple, weekly dialysis treatments. This illustrates the very high burden of celiac disease on patients.

Catassi C; Fabiani E; Iacono G, D’Agate C, Francavilla R, Biagi F et al. A prospective, double blind, placebo controlled trial to establish a safe gluten threshold for patients with celiac disease. Am J Clin Nutr 2007; 85:160-166.

Shah S, Akbari M, Vanga R, et al.Patient perception of treatment burden is high in celiac disease compared with other common conditions. Am J Gastroenterol 2014; 109:1304-1311.

Celiac Disease

When the Diet is Not Enough: Diet Non-Responsive Celiac Disease

Contrary to previous belief, it is now proven that the gluten-free diet (GFD) is not only a burden, but it is also ineffective for many patients. As a result of the difficulty in maintaining total avoidance of gluten while on a GFD, gluten contamination results in 50% or more of all diagnosed celiac patients continuing to have an active disease.

Patients who continue to have symptoms despite attempting to maintain a gluten-free diet are deemed to have diet non-responsive celiac disease. This is defined as persistent symptoms, signs or laboratory abnormalities typical of celiac disease despite 6–12 months of dietary gluten avoidance. The hypotheses to explain the sustained disease activity in many patients on a GFD include the potential for greater sensitivity to gluten in some patients and, particularly, continued gluten exposure given that it is virtually impossible to avoid gluten contamination in modern societies.

Rubio-Tapia A, Hill ID, Kelly CP, Calderwood AH, Murray JA. American College of Gastroenterology. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol 2013; 108:656-676.

Lee SK, Lo W, Memeo L, Rotterdam H, Green PH. Duodenal histology in patients with celiac disease after treatment with a gluten-free diet. Gastrointest Endosc 2003; 57:187-191.

Midhagen G, Hallert C. High rate of gastrointestinal symptoms in celiac patients living on a gluten-free diet: controlled study. Am J Gastroenterol 2003; 98:2023-2026.

Hopper AD, Cross SS, Hurlstone DP, et al. Pre-endoscopy serological testing for coeliac disease: evaluation of a clinical decision tool. Br Med Journal 2007; 334:729.

Cranney A, Zarkadas M, Graham ID, et al. The Canadian Celiac Health Survey. Dig Dis Sci 2007; 52:1087-1095.

When the Diet is Not Enough: Refractory Celiac Disease

While rare (approximately 1 in 200 patients), the most serious complication of celiac disease is the development of a small bowel gastrointestinal T-cell lymphoma after many years of exposure to gluten. This malignant condition, which is no longer dependent of gluten or responsive to a gluten-free diet (GFD), is termed refractory celiac disease Type II (RCD-II). One in two patients with RCD-II will develop enteropathy-associated T cell lymphoma (EATL), which typically has a very poor prognosis and more than 50% mortality in many studies.

The treatment of RCD-II is difficult. Abnormal malignant lymphocytes are scattered in the whole small intestinal epithelium and usually in the stomach and colon, thereby precluding surgery. The prognosis of RCD-II is poor with death occurring within 3-10 years due to intractable diarrhea and/or high-grade lymphomas or, more rarely, metastasis of the low-grade proliferation to other tissues (e.g., skin, lungs). The treatment of high-grade lymphoma relies on surgical resection and chemotherapy, but the prognosis is very poor. An effective treatment for RCD-II remains one of the highest priorities.

Lebwohl B, Granath F, Ekbom A, et al. Mucosal healing and risk for lymphoproliferative malignancy in celiac disease: a population-based cohort study. Ann Intern Med 2013; 159:169-175.

Nijeboer P, de Baaij LR, Visser O, et al. Treatment response in Enteropathy Associated T-cell Lymphoma; survival in a large multicenter cohort. Am J Hematol 2015; 90:493-498.

Celiac Disease

The Role of IL-15 in Celiac and Refractory Celiac

Interleukin 15 (IL-15) is a molecule produced by immune and intestinal cells that is considered to be a central regulator of celiac disease and a driver of lymphoma growth in refractory celiac disease Type II (RCD-II).

In diet non-responsive celiac disease, IL-15 appears to be an essential activation factor for the intra epithelial lymphocytes (IELs), which destroy the gut mucosa.

In RCD-II, IL-15 is increased in the intestinal mucosa and is believe to be involved in the mechanism of the disease.

Abadie V, Jabri B. IL-15: a central regulator of celiac disease immunopathology. Immunol Rev 2014; 260:221-234.

Malamut G, El Machhour R, Montcuquet N, Martin-Lannerée S, Dusanter-Fourt I, Verkarre V, et al. IL-15 triggers an antiapoptotic pathway in human intraepithelial lymphocytes that is a potential new target in celiac disease-associated inflammation and lymphomagenesis. J Clin Invest 2010; 120:2131-2143.

IL-15chart

About Us

Corporate Overview

Celimmune LLC is a clinical development-stage immunotherapy company focused on treating and preventing autoimmune diseases. Our goal is to develop a portfolio of products and technologies targeting autoimmune diseases by leveraging our expertise in translational and rapid go/no-go decision clinical development of high-potential therapeutics.

Our lead product candidate – AMG 714 – is a Phase 2 anti-IL-15 monoclonal antibody that we are developing for the treatment of diet non-responsive celiac disease and Type II refractory celiac disease, a rare type of intestinal lymphoma.

Celiac disease is a chronic hereditary systemic autoimmune and inflammatory disease triggered by gluten consumption, which can cause gastrointestinal dysfunction and debilitating symptoms, including nutritional malabsorption. Over the course of a lifetime, untreated or poorly managed celiac disease is often associated with deteriorating general health, multiple serious intestinal and extra-intestinal medical complications, and increased morbidity and mortality. Celiac disease is the only common autoimmune disease without any approved medication.

We are developing AMG 714 for celiac disease based on scientific research involving IL-15. IL-15 appears to be an essential, non-redundant, growth factor for those intraepithelial lymphocytes that cause intestinal mucosal atrophy and pathological progression to lymphoma in Type II refractory celiac disease. IL-15 has been shown to be one of the key factors in the loss of tolerance to food antigens, and also is believed to be involved in Crohn’s disease and other immune-mediated diseases.

Based on this understanding, we licensed AMG 714 from Amgen (NASDAQ:AMGN). Under the provisions of an exclusive license agreement, Celimmune has the rights to develop, manufacture and commercialize AMG 714 on a worldwide basis, excluding Japan.

About Us

Francisco Leon, M.D., Ph.D.

Co-Founder, Chief Executive Officer & Chief Medical Officer

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Dr. Leon co-founded Celimmune as Chief Executive Officer and Chief Medical Officer, bringing in a breadth of experience from his industry and academic career in the fields of autoimmunity and celiac disease. Prior to founding Celimmune, Dr. Leon served as Vice President and Head of Translational Medicine at Johnson & Johnson’s Janssen Pharmaceuticals (formerly Centocor), where he led early-stage clinical development in immunology. Before joining Janssen in 2010, Dr. Leon served as Chief Medical Officer at Alba Therapeutics, Director of Clinical Development, Inflammation & Respiratory at Medimmune/AstraZeneca, and Director of Clinical Discovery, Immunology & Oncology at Bristol-Myers Squibb.

Prior to joining the biopharma industry, Dr. Leon served as a Research Fellow at the National Institutes for Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH). In 2011, he became an Adjunct Research Associate Professor of Medicine at Jefferson Medical College in Philadelphia, where he continues to contribute to the clinical research efforts of the Department of Gastroenterology.

Dr. Leon is a trained translational immunologist who received his M.D. and Ph.D. from Autónoma University in Madrid, Spain. In his 20 years of experience in translational immunology, Dr. Leon has authored or co-authored more than 75 peer-reviewed articles, book chapters and patents.

Ashleigh Palmer

Co-Founder, Executive Chairman

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Mr. Palmer co-founded Celimmune as Executive Chairman, bringing 30 years of experience in corporate strategy formulation and clinical drug development. Mr. Palmer also serves as the President of Creative BioVentures Corp. (CBV), a strategic advisory firm serving the biopharma industry. Since founding CBV in 2002, Mr. Palmer has advised numerous clients regarding corporate positioning and strategy, fund raising, M&A transactions, clinical development and commercialization, and has undertaken a number of CEO and board level transformational leadership and turnaround assignments for both public and private biopharma companies.

Prior to founding CBV, Mr. Palmer was Vice President, Business Development for British Oxygen’s Ohmeda, Inc., where he was instrumental in its $1.2 billion sale to a Baxter-led consortium by spinning out the company’s inhaled nitric oxide assets as INO Therapeutics, Inc. (now Ikaria). Under his leadership, as founding President and CEO, INO Therapeutics developed and commercialized the world’s first selective pulmonary vasodilator, INOmax®, establishing a time-based pricing, orphan drug franchise, subsequently acquired for $1.6 billion by Madison Dearborn. Earlier in his career, Mr. Palmer held positions of increasing responsibility in sales and marketing management at Reckitt Benckiser.

Educated in the UK, Mr. Palmer received his MBA from the University of Bradford and his BSc. honors in Biochemistry and Applied Molecular Biology from the University of Manchester.

About Us

Core Values

Patient Centric: the patient comes first in everything we do

Science Focused: objective scientific method and penetrating research is a primary decision-making element, enabling rapid translation of medical knowledge

Quality Driven: quality, encompassing patient safety and regulatory compliance, is our imperative

Collaborative: we are voracious networkers and extend our capabilities through long-term partnerships and collaboration

Virtual: we challenge bureaucracy and look to build effective solutions and sustainable value, not unnecessary infrastructure

Strategic: focused on long-term goals and viable optionality

Agility: speed, flexibility, contingency and creativity enables success

Fun and Enjoyment: we work very, very hard but do so with joy, humility and a sense of humor

About Us

Advisory Board

Markku Mäki, M.D., Ph.D., Chairman of Celimmune Advisory Board

Maki

Markku Mäki, M.D., Ph.D., is a pediatric gastroenterologist and Professor of Pediatrics at the University of Tampere, and Chief Physician in the Department of Pediatrics at the Tampere University Hospital in Tampere, Finland. Dr. Mäki earned his medical degree from the University of Turku and his doctoral degree from the University of Tampere.

Dr. Mäki has performed academic and clinical research in celiac disease and small intestine mucosal biology for more than 35 years. He has authored and co-authored more than 300 scientific publications on celiac disease, and has been recognized for his research in 2010 with the Wm. K. Warren Jr. Prize in Celiac Disease in Clinical/Translational Research, San Diego, California.

Dr. Mäki is a permanent member of the Finnish Academy of Science and Letters and the President of Finland has granted him the honor of Knight, First Class, of the Order of the White Rose of Finland in 2006. He has also served as the President of the Finnish Celiac Society and is the chairman of its Medical Advisory Board. He works also as an Advisory Board member for several companies working within celiac disease and has organized several international scientific celiac disease symposia.

Anthony J. DiMarino Jr., M.D.

DiMarino

Anthony J. DiMarino, Jr., M.D., currently serves as the William Rorer Professor of Medicine, Chief of the Division of Gastroenterology and Hepatology at Thomas Jefferson University Hospital in Philadelphia, Pennsylvania. He is also the founder of the first Adult Celiac Center in Philadelphia, which is currently at Thomas Jefferson University Hospital. He received his medical degree from Hahnemann Medical College and completed his internal medicine residency and fellowship in gastroenterology and served on the full-time faculty at the Hospital of the University of Pennsylvania.

Dr. DiMarino’s research interests have primarily been in the areas of esophageal, small intestinal motility, celiac disease and the safety of gastrointestinal endoscopy. He is the author of the “White Paper,” commissioned by the Food and Drug Administration, which remains the standard for reprocessing endoscopic gastrointestinal instruments to protect patient safety between GI Endoscopic procedures. Dr. DiMarino is the author of more than 300 original papers, chapters, and abstracts including his most recent textbook, co-authored with Sidney Cohen, M.D. titled “Extraintestinal Manifestations of GERD” and, along with the Chief of Gastroenterology, Stanley Benjamin, MD, at Georgetown University, “Gastrointestinal Disease, An Endoscopic approach” which is in its second edition.

Dr. DiMarino has been honored as “Physician of the Year” by the Delaware Valley Chapter of the Crohn’s & Colitis Foundation of America and as a “Top Doc” in Philadelphia Magazine from 1991 through 2015. In 2006 through 2015 he was named by Castle Connolly Medical Ltd. as one of America’s “Top Doctors.” In 2012, he was one of six appointed to the National United Healthcare Gastrointestinal Scientific Advisory Board, as well as to the Thomas Jefferson University Hospital Board of Trustees.

Dr. Ciarán P. Kelly, M.D.

Kelly

Dr. Ciarán P. Kelly, M.D. is Professor of Medicine at Harvard Medical School and Director of Gastroenterology Training at Beth Israel Deaconess Medical Center, Boston, Massachusetts USA. Dr. Kelly earned his medical degree from Trinity College in Dublin, Ireland where he was a Foundation Scholar and recipient of numerous academic awards. Dr. Kelly has also received postgraduate clinical and research awards from the Crohn’s and Colitis Foundation of America, the American Gastroenterological Association and the National Institutes of Health. He is an American Gastroenterology Association Fellow and a Fellow of the American College of Gastroenterology.

Dr. Kelly has engaged in patient care and research in Celiac disease for more than 20 years. In 2004 he was a founder of the Celiac Center at BIDMC and serves as its Director. In 2013 he co-founded the Celiac Research Program at Harvard Medical School.

Dr. Kelly is an internationally recognized expert in the diagnosis and management of celiac disease and, in his clinical practice, specializes in difficult-to-treat enteropathy. He also leads research programs on the pathogenesis of celiac disease, its diagnosis and new approaches to treatment. He has served as a committee member of the NIH, Center for Scientific Review as well as FDA, CDC and NIH committees on celiac disease and C. difficile infection. Dr. Kelly is the author of more than 200 clinical and basic research book chapters, invited reviews, and original research articles appearing in medical and scientific journals including Gastroenterology, Vaccine, Infection & Immunity, The Journal of Clinical Investigation, The Lancet, and The New England Journal of Medicine.

Bana Jabri, M.D., Ph.D.

Jabri

Bana Jabri, M.D. Ph.D. is one of the leading researchers of celiac disease in the world and has directed the research team at The University of Chicago Celiac Disease Center since 1999. With her leadership, the University of Chicago Celiac Disease Center research team continues to make great strides in determining what triggers the abnormal reaction to gluten in celiac disease.

Dr. Jabri is a professor in the Departments of Medicine, Pathology and Pediatrics at the University of Chicago Medical Center, and is a member of the Committee on Immunology. She is Director of Research of the University of Chicago Celiac Disease Center, the Co-director of the University of Chicago Digestive Disease Research Core Center (one of the 17 NIH sponsored Centers of Excellence for Digestive Disease Research in the United States) and the Vice Chair for Research in the Department of Medicine.

Dr. Jabri completed her residency in pediatric gastroenterology in 1991 at the Assistance Publique Hopitaux de Paris, and her Ph.D. in immunology at the University Paris, VII in 1996. From 1999 to 2002, Dr. Jabri worked in research at Princeton University, after which she joined the University of Chicago. During this period, she was member of the Gastroenterology Mucosal Pathobiology National Institute of Health and Crohn’s and Colitis Foundation study sections.

She has co-authored numerous high impact articles in peer-reviewed publications on celiac disease, mucosal immunology and IL-15. She has also been awarded the coveted Warren Prize for Excellence in Celiac Disease Research—a first for anyone in the United States, was elected to the Kunkel Society and the Association of American Physicians. One of Dr. Jabri’s most recent discoveries led to the initiation of Celimmune’s clinical trials aimed at targeting IL-15 in refractory celiac disease.

Joseph A. Murray, M.D.

Murray

Born in Ireland, Joseph A. Murray, M.D. attended medical school at the National University of Ireland in Galway, followed by internal medicine training at Trinity College in Dublin and internal medicine and gastroenterology training at Beaumont Hospital in Dublin. He further trained at the University of Iowa as a Fellow in Gastroenterology and Hepatology, and earned his Doctorate of Medicine by thesis from the National University of Ireland in Galway in 1992.

Dr. Murray leads a large celiac disease program in the upper Midwest. He has a strong background and experience in basic and clinical gastroenterology, focusing primarily on celiac disease and immune-related disorders of the small intestine. He is a member of many national/international professional scientific committees and review boards, including membership in the Gastrointestinal Mucosal Pathobiology Study Section of the National Institutes of Health. He has served on editorial boards of several journals and is a senior associate editor for the American Journal of Gastroenterology.

He is the author/co-author of more than 220 scientific publications and 30 chapters. His work is funded by the NIH, private foundations and commercial entities. He is a past president and founding member of the North American Society for the Study of Celiac Disease, a fellow of the American Gastroenterologic Association and American College of Gastroenterology and a member of American Association of Immunology, American Motility Society, and serves on advisory boards for lay support groups and consults with several companies on the topic of celiac disease. His current work spans basic and translational research in the realm of celiac disease focusing on immunology, genetics of the disease and immune responses to food proteins.

About Us

Strategic Partners

Celimmune has in-licensed AMG 714 from Amgen (NASDAQ:AMGN)

Amgen

More details about Celimmune’s AMG 714 license transaction can be found at www.amgenbd.com

We count on the support of a trusted network of collaborators, including:

2LPharma

2LPharmawww.2Lpharma.com

Biomedal, S.L.

Biomedalwww.biomedal.com