Exvastat

IMPACT CASE STUDIES

SAVING LIVES BY IMPROVING THE TREATMENT OF ARDS FROM ANY CAUSE

IMP RATING: B – BENEFIT STAKEHOLDERS Exvastat is developing a pioneering new treatment for Acute Respiratory Distress Syndrome. We are immensely grateful to CIC for their belief in the underlying science, their support in building the corporate infrastructure to allow the company to grow, their input to the development programme and for their continued financial support to the company through its journey.

DAVID CAVALLA

CEO

We have applied the Impact Management Project (IMP) framework (see IBC for further details) in summarising the impact of a selection of our investments.

COMPANY DESCRIPTION

Exvastat is a clinical-stage drug development company, developing Impentri®, an intravenous formulation of Imatinib, as a treatment for all-cause Acute Respiratory Distress syndrome (ARDS) including ARDS related to COVID-19 infection.

IMPACT THESIS

ARDS is a severe, life-threatening medical condition characterised by widespread inflammation, damage to the pulmonary endothelium and consequent fluid accumulation in the lungs. Every year, moderate-severe variants of this condition affects more than 200,000 people in Europe alone. With a case fatality rate of 40–55% and no approved pharmacotherapy, there is a huge unmet medical need. Based on original work by Vrije Universiteit in Amsterdam, a novel mechanism of action was discovered for imatinib, the tyrosine kinase inhibutor which causes an increase in the cell-cell adhesion of pulmonary endothelial cells. When administered to patients with ARDS, it has been shown that imatinib may improve the integrity of the pulmonary endothelium and decrease the impact of pulmonary oedema. Patients with moderate-severe ARDS are typically anaesthetised in order to facilitate the enhancement of ventilation mechanically. Exvastat has created the first stable formulation of imatinib, Impentri®, that can be delivered intravenously to anaesthetised patients receiving mechanical ventilation.

IMPACT SUMMARY

In a recently published randomised, placebo-controlled study (CounterCOVID) in patients with acute respiratory distress associated with COVID-19 infection, the use of oral imatinib was associated with a 47% reduction in mortality rate at Day 28. This benefit was on the background of standard of care including the use of dexamethasone in 70% of patients. If these findings are confirmed in further studies in patients with all cause moderate-severe ARDS, the intravenous formulation of imatinib (Impentri®) that Exvastat is developing would have a significant impact on the morbidity and mortality of this devastating condition. Pricing has not yet been determined but it is noted that the patent covering the use of imatinib in ARDS only covers US and Europe; it is expected that pricing in less developed parts of the world which are not covered by patent protection will be affordable. In addition to the reduction in mortality, the CounterCOVID study demonstrated that imatinib was associated with a reduction in stay on the Intensive Care Unit and a reduction in the duration of mechanical ventilation. If these findings are confirmed in larger studies, the healthcare costs of managing patients with ARDS would be substantially reduced. Furthermore, there are considerable long-term morbidities in survivors of ARDS. Should Impentri® be shown to reduce the intensity of the condition, it is anticipated that survivors would benefit from improved long-term functionality. This thesis will be investigated in the proposed Phase 3 studies. Should the hoped-for reduction in mortality and morbidity associated with the use of Impentri® be confirmed in larger studies, the impact of reduced morbidity and mortality on stakeholders whether they are patients, their families or wider society in which the patients live, would be substantial. CIC has been the sole institutional investor in Exvastat and has provided considerable help on the corporate governance of the company and input on the preclinical and clinical development of Impentri®. Although another investor may have been found to support the company in this important field, there would have been a risk that the company would not have received the same level of support through its journey as CIC has provided. The initial results from the CounterCOVID study are very promising but need to be confirmed both in patients with COVID-19 infection, but also in the wider population with all-cause ARDS. The history of clinical development is littered with programmes where early results have not been replicated in later studies and although the extensive work on the mechanism of action and the highly promising results in a robust and reasonably large (n=385) CounterCOVID study are highly promising, the development risks remain significant.