Pipeline

Immunic is currently pursuing three development programs. These include the IMU-838 program, which is focused on the development of oral formulations of small molecule inhibitors of the enzyme dihydroorotate dehydrogenase, or DHODH; the IMU-935 program, which is focused on an inverse agonist of RORγt, an immune cell-specific isoform of retinoic acid receptor-related orphan nuclear receptor gamma, or RORγ, and the IMU-856 program, which involves 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 markets, these products are also being developed to address certain rare diseases with high unmet medical needs, such as primary sclerosing cholangitis, and Guillain-Barré syndrome. Immunic is also investigating IMU-838 as a potential treatment option for COVID-19.

pipeline Immunic Therapeutics

An additional investigator-sponsored phase 2 clinical trial of IMU-838 in combination with oseltamivir in patients with moderate-to-severe COVID-19 is ongoing in collaboration with the University Hospitals Coventry and Warwickshire NHS Trust, UK.

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 and damaged by the immune system. 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 RRMS, the most common form of MS. Approximately 85% of patients with MS are expected to develop RRMS, with some of these patients later developing more progressive forms of the disease. RRMS is characterized by clearly defined attacks of new or increasing neurologic symptoms. These relapses are followed by periods of remissions, 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 in the prime working age, peaking around 30 years old, 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] MS affects twice as many women and men in certain age cohorts and is more common in areas inhabited by people of northern European ancestry, such as Europe, the United States, Canada, New Zealand and parts of Australia.

Indication: Ulcerative Colitis

Ulcerative colitis, or UC, is most commonly diagnosed in late adolescence or early adulthood, but it 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 that there 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].

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.

Indication: Crohn’s disease

Crohn’s disease, or CD, is an idiopathic chronic inflammatory disease of unknown etiology with genetic, immunologic and environmental influences. Like UC, it is one of the major diseases that are generally characterized as IBD. Both UC and CD are caused by chronic inflammation in the gastrointestinal, or GI, tract, but CD can involve the entire GI 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. Distinguishing CD from UC can be challenging when inflammation is confined to the colon. CD typically involves all layers of the bowel wall, thereby causing complications such as abscesses, strictures and fistulas that regularly require surgical intervention.

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 it can manifest at any age. According to recent data and literature reviews on the incidence of CD, 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: COVID-19

The World Health Organization declared severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2, infections causing COVID-19 a pandemic on March 11, 2020[8]. At present, the total number of cases is difficult to accurately quantify but continues to rise and has grown to more than 100,000,000 cases globally[9].

Main clinical symptoms include fever, cough, myalgia or fatigue, expectoration, and dyspnea[10], however a range of other symptoms have been connected to COVID-19 as well. While a majority of patients do not experience severe symptoms, one meta-analysis found that approximately 18 % of cases were severe[11]. The symptoms of COVID-19 typically appear within 3 to 14 days after initial exposure to SARS-CoV-2. If any patient develops characteristic symptoms of COVID-19 or was exposed to a person with COVID-19 disease, infection with SARS-CoV-2 leading to COVID-19 has to be considered. As there are no specific clinical features that can reliably distinguish COVID-19 from other viral respiratory infections, the patient will then need to undergo specific testing for SARS-CoV-2.

Although several testing methods have been developed, polymerase chain reaction, or PCR, testing remains the primary and most reliable COVID-19 diagnostic testing method in the United States and in most developed countries. Generally, a sample from the nose (nasopharyngeal swab) or throat (throat swab) is taken and then sent to a laboratory for testing.

Indication: Primary Sclerosing Cholangitis

Primary sclerosing cholangitis, or 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[12]. 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[13]. 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[13].

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[14]. The disease prevalence varies between geographic regions. Studies of psoriasis suggest an overall prevalence of 2% to 3% of the world’s population, with a higher prevalence 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 a second peak between 50 and 60 years of age.

Indication: Guillain Barré Syndrome

Historically, Guillain Barré syndrome, or GBS, was considered a single disease entity. It is now known to be a heterogeneous syndrome with several variant forms. Acute inflammatory demyelinating polyradiculopathy, or AIDP, is the most common form in North America, Europe and most of the developed world, where it accounts for approx. 90% of cases. GBS is thought to result from an immune response to a preceding infection that cross-reacts with peripheral nerve components. The exact mechanisms are unknown. However, cellular and humoral immune responses are of relevance in the pathogenesis of GBS.

The clinical manifestation of GBS is characterized by an acute or subacute onset of a progressive, symmetric weakness in limbs or cranial nerve-innervated muscles, accompanied by absent or depressed deep tendon reflexes, and a characteristic profile in the cerebrospinal fluid and electrodiagnostic studies[15]. Patients usually present a few days to a week after onset of symptoms. The weakness can vary from mild difficulty with walking to nearly complete paralysis of all extremity, facial, respiratory, and bulbar muscles.

GBS occurs worldwide with an overall incidence of 0.16 to 3.0 per 100,000 person-years[16]. Thus, it is considered a rare disease. The incidence increases by approx. 20% with every 10-year increase in age beyond the first decade of life[17]. In addition, the incidence is slightly greater in males than in females.

[1] Wallin MT, Culpepper WJ, Campbell JD, Nelson LM, Langer-Gould A, Marrie RA, et al. The prevalence of MS in the United States: A population-based estimate using health claims data. Neurology. 2019;92(10):e1029–40
[2] Green J, Dunn WH, Medical Review(s), Application Number: 202992Orig1s000, 25 August 2012. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202992Orig1s000StatR.pdf
[3] Burisch J, Munkholm P. The epidemiology of inflammatory bowel disease. Scand J Gastroenterol. 2015;50(8):942–51.
[4] Hanauer SB. Inflammatory bowel disease: Epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis. 2006;12:S3–9.
[5] Burisch J, Jess T, Martinato M, Lakatos PL, ECCO -EpiCom. The burden of inflammatory bowel disease in Europe. J Crohns Colitis. 2013;7(4):322–37.
[6] Longobardi T, Bernstein CN, Bitton A, Panaccione R, Glasgow K, Tolomiczenko G. The Burden of Inflammatory Bowel Disease (IBD) in Canada. In: Crohn’s and Colitis Foundation of Canada [conference paper]; 2014 June 10. Available from: https://www.researchgate.net/publication/216221892
[7] Kappelman MD, Rifas-Shiman SL, Kleinman K, Ollendorf D, Bousvaros A, Grand RJ, et al. The prevalence and geographic distribution of Crohn’s disease and ulcerative colitis in the United States. Clin Gastroenterol Hepatol. 2007;5(12):1424–9.
[8] World Health Organization. WHO Director-General’s opening remarks at the media briefing on COVID-19 – 11 March 2020 [document on the Internet]; 2020 March 11. Available from: https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19—11-march-2020
[9] Johns Hopkins University & Medicine (2020): Coronavirus COVID-19 Global Cases by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU) [document on the Internet]. Available from: https://coronavirus.jhu.edu/map.html
[10] Li L-Q, Huang T, Wang Y-Q, Wang Z-P, Liang Y, Huang T-B, et al. COVID-19 patients’ clinical characteristics, discharge rate, and fatality rate of meta-analysis. J Med Virol. 2020;92(6):577–83.
[11] Sun P, Qie S, Liu Z, Ren J, Li K, Xi J. Clinical characteristics of hospitalized patients with SARS-CoV-2 infection: A single arm meta-analysis. J Med Virol. 2020;92(6):612–7.
[12] Toy E, Balasubramanian S, Selmi C, Li C-S, Bowlus CL. The prevalence, incidence and natural history of primary sclerosing cholangitis in an ethnically diverse population. BMC Gastroenterol. 2011;11:83.
[13] Singh S, Talwalkar JA. Primary sclerosing cholangitis: diagnosis, prognosis, and management. Clin Gastroenterol Hepatol. 2013;11(8):898–907.
[14] Di Meglio P, Villanova F, Nestle FO. Psoriasis. Cold Spring Harb Perspect Med. 2014;4(8):a015354.
[15] Hughes RAC, Cornblath DR. Guillain-Barré syndrome. Lancet. 2005;366(9497):1653–66.
[16] McGrogan A, Madle GC, Seaman HE, de Vries CS. The epidemiology of Guillain-Barré syndrome worldwide. A systematic literature review. Neuroepidemiology. 2009;32(2):150–63.
[17] Sejvar JJ, Baughman AL, Wise M, Morgan OW. Population incidence of guillain-Barré syndrome: A systematic review and meta-analysis. Neuroepidemiology. 2011;36(2):123–33.