R&D Portfolio

Acute Pancreatitis

 Acute pancreatitis is an inflammatory condition characterized by abdominal pain and elevated levels of pancreatic enzymes, which injure pancreas tissue and lead to dysfunction of the gland, as well as remote organs and systems. A systematic review estimated that >50% of pancreatitis cases are smoking-related, almost 25% of cases were related to abnormal weight, and nearly 20% were related to excessive alcohol consumption. The review also emphasized that consumption of vegetables and fruits is associated with a nearly 30% risk reduction (1). Hospitalization costs for acute pancreatitis Patients in the United States were estimated to be as high as USD 30.000 per patient (2), with more than USD 2 billion annual costs for the US health care system.

The incidence of acute pancreatitis varies widely between countries, and studies. A review of high quality studies defined an average of ~34 cases per 100,000 person-years (3). An annual increase of ~3% across countries, between 1961 and 2016, may be associated with increases in metabolic syndrome and obesity, and a higher resulting frequency of gallstone disease, which is a critical inducer of acute pancreatitis (2). There is currently no pharmacotherapy for acute pancreatitis on the market.

Severe burn and smoke inhalation injuries

Each year more than 180.000 people die from burn-related injuries (4). Millions more suffer from burn-related disabilities and disfigurements which have psychological, social and economic effects on both the survivors and their families. Major burn injuries lead to prolonged and expensive hospital stays. In addition to pain management and wound care, these patients require nutritional support, and are at risk to acquire secondary  infections, due to suppression of the immune system. 

In the USA, the average hospital fee for care of a child with extensive third-degree burns requiring skin grafting was more than USD 140.000 (5).

The incidence of burn and smoke inhalation with major injury varies between countries, with the incidence for major injury ranging per 100.000 person-years between 10 in the USA, to ~30 in Europe (5). 

While many products and techniques are available for managing cutaneous thermal trauma, few pharmaceutical options are under investigation for the stabilization of patients that sustained major burn-related injuries.

A significant challenge is the preparedness for, and treatment of burn injuries in austere settings, i.e. in situations of civilian mass casualty events, where resources are limited, or in military combat, where extraction of the injured for definitive treatment can be delayed and problematic (6, 7). Ideally treatments to be used under these circumstances should be easy to use and store, and could counteract physiological effects of undebrided burns, such as inflammation, burn progression and delayed healing. 

Sepsis

Sepsis is estimated to affect 50 million people per year worldwide and may cause 11 million deaths (8). According to the Global Sepsis Alliance, mortality varies by country, between 15% and over 50%. Many sepsis survivors suffer long-lasting consequences.

In conjunction with effective antimicrobial treatments, a pharmaceutical targeting the inappropriate immune response that causes organ failure in sepsis could help to save lives, and to mitigate the debilitating effects of sepsis for survivors

The ApoGlyx lead compound RG100204 has demonstrated remarkably robust effects, protecting from organ damage in a clinically relevant in vivo model of bacterial infection, systemic inflammation, and multi-organ dysfunction (9).

Further reading

1. Alsamarrai, A., Das, S. L., Windsor, J. A., andPetrov, M. S. (2014) Factors that affect risk for pancreatic disease in the general population: a systematic review and meta-analysis of prospective cohort studies Clin Gastroenterol Hepatol 12, 1635-1644 e1635; quiz e1103 10.1016/j.cgh.2014.01.038

2. Iannuzzi, J. P., King, J. A., Leong, J. H., Quan, J., Windsor, J. W., Tanyingoh, D. et al. (2022) Global Incidence of Acute Pancreatitis Is Increasing Over Time: A Systematic Review and Meta-Analysis Gastroenterology 162, 122-134 10.1053/j.gastro.2021.09.043

3. Xiao, A. Y., Tan, M. L., Wu, L. M., Asrani, V. M., Windsor, J. A., Yadav, D. et al. (2016) Global incidence and mortality of pancreatic diseases: a systematic review, meta-analysis, and meta-regression of population-based cohort studies Lancet Gastroenterol Hepatol 1, 45-55 10.1016/S2468-1253(16)30004-8

4. Yin, B., He, Y., Zhang, Z., Cheng, X., Bao, W., Li, S. et al. (2023) Global burden of burns and its association with socio-economic development status, 1990–2019 Burns : journal of the International Society for Burn Injuries 10.1016/j.burns.2023.02.007

5. Peck, M., Molnar, J., andSwart, D. (2009) A global plan for burn prevention and care Bull World Health Organ 87, 802-803 10.2471/blt.08.059733

6. Young, A. W., Graves, C., Kowalske, K. J., Perry, D. A., Ryan, C. M., Sheridan, R. L. et al. (2017) Guideline for Burn Care Under Austere Conditions: Special Care Topics J Burn Care Res 38, e497-e509 10.1097/BCR.0000000000000369

7. Bennett, B. L., Butler, F. K., Jr., andWedmore, I. S. (2017) Tactical Combat Casualty Care: Transitioning Battlefield Lessons Learned to Other Austere Environments Wilderness Environ Med 28, S3-S4 10.1016/j.wem.2017.01.003

8. Rudd, K. E., Johnson, S. C., Agesa, K. M., Shackelford, K. A., Tsoi, D., Kievlan, D. R. et al. (2020) Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study Lancet 395, 200-211 10.1016/S0140-6736(19)32989-7

9. Mohammad, S., O’Riordan, C. E., Verra, C., Aimaretti, E., Alves, G. F., Dreisch, K. et al. (2022) RG100204, A Novel Aquaporin-9 Inhibitor, Reduces Septic Cardiomyopathy and Multiple Organ Failure in Murine Sepsis Front Immunol 13, 900906 10.3389/fimmu.2022.900906