Immunic is currently pursuing three development programs. These include the IMU-838 program, focused on the development of oral formulations of small molecule inhibitors of dihydroorotate dehydrogenase, or DHODH; the IMU-935 program, focused on an inverse agonist of RORgt, an immune cell-specific isoform of RORg (retinoic acid receptor-related orphan nuclear receptor gamma); and the IMU-856 program, involving the development of a drug targeting the restoration of intestinal barrier function. These product candidates are being developed to address diseases such as relapsing-remitting multiple sclerosis, ulcerative colitis, Crohn’s disease, and psoriasis. In addition to these large market opportunities, Immunic’s products are also being developed to address certain rare diseases with high unmet medical needs, such as primary sclerosing cholangitis.

Indication: Multiple Sclerosis

Multiple sclerosis, or MS, is an autoimmune disease that affects the brain, spinal cord and optic nerve. In MS, myelin, the coating that protects the nerves, is attacked by immune cells and damaged. Thus, MS is considered an immune-mediated demyelinating disease of the central nervous system, or CNS. MS is a progressive disease, which, without effective treatment, leads to severe disability.

Immunic is developing IMU-838 for the treatment of relapsing-remitting MS, or RRMS, the most common form of the disease. Approximately 85% of patients with MS are expected to develop RRMS, with some of these patients later developing other and more severe forms. RRMS is characterized by clearly defined attacks of new or increasing neurologic symptoms, followed by periods of remission, or partial or complete recovery. During remissions, all symptoms may disappear, or some symptoms may continue and become permanent. MS is a disease with unpredictable symptoms that can vary widely. Common early signs of MS include vision problems, tingling and numbness or other unspecific neurological symptoms. Diagnosis of MS is confirmed via blood tests and a spinal tap, in which a small sample of fluid is removed from the spinal cord. However, most important for diagnosis are characteristic CNS lesions found using magnetic resonance imaging, or MRI.

MS affects more than 700,000 people in the United States, and more than 2.2 million people worldwide.[1] The disease has a large economic impact as it affects mainly young adults of prime working age, although MS can occur in children and in adults. MS is at least two to three times more common in women than in men.[2]

Indication: Ulcerative Colitis

Ulcerative colitis, or UC, is a chronic inflammatory disease characterized by diffuse inflammation of the mucosa of the colon and rectum. The hallmark clinical symptoms of UC are diarrhea and bloody stool, and its clinical course is marked by exacerbations and remissions, which may occur spontaneously or in response to treatment changes or intercurrent illnesses.

UC is most commonly diagnosed in late adolescence or early adulthood, but can occur at any age. The occurrence of UC worldwide has increased over the past few years[3], particularly in Latin America, Asia and Eastern Europe. Recent estimates note thatthere are more than 700,000 patients affected by UC in the United States[4], as well as 1.5 million in Europe[5] and more than 100,000 in Canada[6]. UC is almost equally distributed between genders.[7]

Indication: Crohn’s disease

Crohn’s disease, or CD, is an idiopathic chronic inflammatory disease of unknown etiology with genetic, immunologic and environmental influences. Both UC and CD are caused by chronic inflammation in the gastrointestinal tract, but CD can involve the entire gastrointestinal tract, from the mouth to the anus (but it most commonly involves both the large and small intestines), whereas UC is restricted to the colon and rectum. Hallmark clinical symptoms of CD are chronic diarrhea and abdominal pain. However, the diagnosing physician needs to evaluate laboratory tests, endoscopy results, pathology findings and radiographic tests to arrive at a clinical diagnosis of CD. In general, it is the presence of chronic intestinal inflammation that leads to a diagnosis of CD.

CD is most commonly diagnosed in late adolescence or early adulthood, but can manifest at any age. Recent estimates note that there are more than 600,000 patients affected by CD in the United States[4], as well as 1.1 million in Europe[5] and more than 125,000 in Canada[6]. CD is slightly more prevalent in women than in men.[7]

Indication: Primary Sclerosing Cholangitis

PSC is a rare liver disease in which the bile ducts in the liver become inflamed, narrow and prevent bile from flowing properly. PSC has a prevalence of approximately 4.15 per 100,000 in the United States[8]. The exact cause and disease mechanism of PSC are still unknown, but an autoimmune mechanism may play a role. There is an association with IBD, most often with UC and less commonly with CD. Progressive biliary and hepatic damage results in portal hypertension and hepatic failure in a significant majority of patients over a 10–15 year period from initial diagnosis.[9]

Indication: Psoriasis

Psoriasis is a chronic inflammatory disease of the skin with unknown etiology that leads to hyperproliferation of keratinocytes and endothelial cells. Most mechanistic data support the hypothesis that psoriasis is an autoimmune disease driven by activated T-lymphocytes which then release cytokines, chemokines and pro-inflammatory molecules into the dermis and epidermis. Psoriasis is characterized clinically by development of red, scaly, itchy, symmetrical, dry plaques typically located on skin overlying the elbows, knees, lumbar area, and scalp. Plaques vary from a few millimeters in diameter to several centimeters and can be localized to a specific area or extend over most of the body surface.

Psoriasis is one of the most common chronic inflammatory skin diseases. The disease prevalence varies between geographic regions. Studies of psoriasis[10] suggest an overall prevalence of 2% to 3% of the world’s population, with a higher incidence in U.S. and Canadian populations (4.6% and 4.7% respectively). Psoriasis is considered equally prevalent between genders and can occur at any age. However, there seems to be a bimodal distribution of the age of disease onset, with a first peak between 15 and 30 years, and the second peak between 50 and 60 years of age.

[1] Wallin M. T., Culpepper W. J., Campbell J. D. et al., Neurology, published online February 15, 2019.
[2] Green J. E., Dunn W. H., Medical Review(s), Application Number: 202992Orig1s000, 25 August 2012.
[3] Burisch, J. & Munkholm, P. (2015), Scandinavian Journal of Gastroenterology, 50:8, 942-951.
[4] Hanauer S. 2006;12:S3-9 (Suppl 1), Kappelmann MD et al., Clin Gastroenterol Hepatol. 2007; 5:1424-9.
[5] Burisch et al., Journal of Crohn’s and Colitis, 2013 7, 322–337.
[6] The Burden of IBD in Canada, www.ccfc.ca. Accessed 16 May 2014.
[7] Kappelman et al., Clin Gastroenterol Hepatol. 2007;5:1424–1429.
[8] Toy et al., BMC Gastroenterology, 2011, 11:83.
[9] Singh et al., Clin Gastroenterol Hepatol. 2013 Aug;11(8):898-907.
[10] Di Meglio, P.; Villanova, F.; Nestle, F.O., Cold Spring Harb. Perspect. Med. 2014 Aug 1;4(8).