Developing sevuparin to help patients with severe conditions and high unmet medical need.
Modus Therapeutics is a Swedish biotech company developing sevuparin for diseases with high unmet medical need. The Company’s near-term focus is to develop sevuparin for patients with sepsis/septic shock, a severe and often fatal condition.
In sepsis/septic shock, an infection has transformed into severe uncontrolled systemic inflammation, which damages blood vessels leading to loss of organ function. Pre-clinical data with sevuparin suggests that it can provide benefit by protecting blood vessels in such circumstances1. Uncontrolled systemic inflammation is a deadly complication of multiple severe medical conditions such as major trauma and surgery, autoimmunity, and viral infection as well as sepsis/septic shock. ‘Systemic inflammatory response syndromes’ (SIRS) is a general clinical definition of the uncontrolled inflammation seen in these situations. The clinical development of sevuparin in sepsis/septic shock may also branch into other indications under this systemic inflammation umbrella.
Sevuparin, has the multimodal mechanism of action that is typical of heparinoids allowing it to target and neutralize the processes that underlie many serious conditions. However, as sevuparin has been designed to have a much-reduced anti-coagulant activity it can be dosed without concern for the bleeding risk. This enhances the potential of sevuparin to deliver the non-anticoagulant benefits of heparinoid to patients across multiple serious conditions. As a result, Modus is currently evaluating further potential indications for sevuparin beyond the ones encompassed by systemic inflammation.
Modus is backed by Karolinska Development (Nasdaq Stockholm: KDEV), KDev Investments AB, (part of Karolinska Development AB and Rosetta Capital), The Foundation for Baltic and European Studies (Östersjöstiftelsen) and Praktikerinvest AB. Different possibilities to finance Modus’ further development of Sevuparin in Sepsis/Septic shock are under active exploration.
1Rasmuson et al, 2019
Sevuparin, our lead product, is a clinical stage, innovative proprietary polysaccharide drug with a multimodal mechanism of action, including anti-inflammatory, anti-adhesive and anti-aggregate effects.
Sevuparin was designed to have markedly reduced anti-coagulant activity. This allows several-fold higher doses to be given, compared to regular mainstream anticoagulants, without the associated risk of unwanted bleeding.
Sevuparin’s combination of anti-inflammatory effects and reduced anticoagulation effects, which enables much higher dosing, gives it the potential to positively impact the treatment of sepsis/septic shock and other conditions where systemic inflammation is involved. These are leading causes of death in intensive care units worldwide, as exemplified by septic shock with mortality rates typically exceeding 30%2.
Sevuparin has been approved for clinical research in both US and Europe. Clinical experience with sevuparin in 145 healthy volunteers and patients with malaria or sickle cell disease has already confirmed the product’s strong safety profile.
Two routes of administration of sevuparin are currently being developed – an IV formulation for in-patient administration and a subcutaneous formulation that allows ambulatory and home care administration.
2 Umegakiet al 2011
Severe systemic inflammation (also known as systemic inflammatory response syndrome, SIRS) is a feared complication of severe medical conditions such as sepsis, trauma, and major surgery. It is characterized by an uncontrolled systemic inflammatory response that can progress into shock and multi-organ failure. Septic shock, the most severe form of sepsis, is a leading cause of death in intensive care units worldwide, with mortality rates typically exceeding 30%3.
Vascular hyper-permeability caused by inflammatory activation, may cause significant endothelial damage, plasma leakage and excessive edema formation. The pulmonary circulation is particularly vulnerable, leading to respiratory distress, and in time more advanced multi-organ damage ensues. Neutrophil granulocytes, releasing an array of cationic proteins exhibiting permeability–increasing properties, are critically involved in the capillary-alveolar barrier breakdown.
There is currently no pharmaceutical product available that can be specifically used to treat patients with uncontrolled systemic inflammation. The current standard of care for hospitalized patients relies on aggressive fluid therapy, vasopressors, oxygen, corticoid steroids, and mechanical ventilation.
Sepsis, a common form of severe systemic inflammation, is one of the costliest conditions to treat in the hospital care setting4. In the US in-patient care cost a total of $23 billion in 2019, a figure that has increased from the $17 billion in 2012. Additional data from the UK estimates the direct cost of treating patients with sepsis in intensive care was £0.8 billion in 2017, while the broader costs to society, including indirect costs, amounted to £10 billion (YHEC The Cost of Sepsis Care, the UK Final Report 2017).
3Umegakiet al, 2011
4 Rudd et al, 2020
Sepsis and septic shock
Sepsis is a condition with uncontrolled systemic inflammation, which becomes a life-threatening and overwhelming response to an infection due to the immune system overreacting and damaging blood vessels, resulting in significant damage to tissues and organs.
As an infection transforms into severe uncontrolled systemic inflammation, sepsis progresses to septic shock, the most severe form, diagnosed when blood pressure drops to dangerous levels. The current standard of care in sepsis patients is limited to early treatment with antibiotics and administration of fluids, oxygen, and vasopressors (hemodynamic support), followed eventually by corticoid steroids and mechanical ventilation.
Sevuparin, due to its multimodal mechanism of action, has the potential to neutralize and balance harmful processes in this disorder, since preclinical data suggests that sevuparin protects the blood vessels during septic inflammatory circumstances by interfering with harmful agents generated by white blood cells 5.
5 Rasmuson et al, 2019
Leadership Team & Board
Modus Therapeutics also acknowledges and thanks all its founders for their continuing support.