Preventing the Progression
EDP1815 May Offer Benefits to Patients at Risk of Developing Severe Complications
How EDP1815 Could Work in COVID-19
Although the body’s immune response is important to fight COVID-19, progression of the disease is associated with hyperinflammation, including the exaggerated immune response caused by the “cytokine storm,” which may lead to life-threatening complications of the virus. During a cytokine storm, the immune system goes into overdrive and a surge of immune cells flood the lungs, resulting in devastating effects, including death, in the most severe cases.
EDP1815 – Evelo’s lead inflammation program – has the potential to modulate multiple immune pathways associated with hyperinflammation and cytokine storm to resolve inflammation and return the body to a state of immune homeostasis, without causing complete immunosuppression or making patients more susceptible to infection.
Disease Progression Infographic
Source: Siddiqi, Hassan K., and Mandeep R. Mehra. “COVID-19 Illness in Native and Immunosuppressed States: A Clinical-Therapeutic Staging Proposal.” The Journal of Heart and Lung Transplantation, 20 Mar. 2020, Elsevier Inc., Figure 1, doi: https://doi.org/10.1016/j.healun.2020.03.012
It is believed that by intervening at earlier stages of disease to prevent or dampen hyperinflammation and the cytokine storm, we can potentially prevent progression to serious COVID-19 and its critical complications
EDP1815’s unique mechanism of action links small intestinal mucosal immunity to systemic inflammation. It appears to be a direct immunomodulator, inducing systemic inflammation resolution. EDP1815 acts on cells in the lining of the small intestine, which then signal throughout the body, even though it has not been detected outside the gut.
Clinical Trial Updates
TACTIC-E is a Phase 2/3 platform trial sponsored by Cambridge University Hospitals NHS Foundation Trust in the United Kingdom (UK). The trial will enroll up to 469 patients per arm who are hospitalized with COVID-19 and are still at early stages of the disease but have multiple risk factors for developing severe complications and are at risk of progression to the intensive care unit or death. Eligible patients will be randomized equally to either one of the active arms or treated with standard of care alone. Patients in arm 1 will be dosed with EDP1815 in addition to standard of care; patients in arm 2 will be dosed with ambrisentan and dapagliflozin in addition to standard of care; and patients in arm 3 will be treated with standard of care only. Interim data from the trial is expected in 4Q 2020.
In collaboration with Rutgers University and Robert Wood Johnson University Hospital, Evelo has submitted an IND for EDP1815-205, a Phase 2 double-blind placebo-controlled study evaluating the safety and efficacy of EDP1815 for the treatment of hospitalized patients with newly diagnosed COVID-19. The study will initially evaluate 60 patients to determine whether early intervention with EDP1815 can prevent progression of COVID-19 symptoms and the development of COVID-Related Complications (CRC)*. The study will be led by Reynold A. Panettieri, Jr., M.D., Vice Chancellor for Translational Medicine and Science at Rutgers Biomedical and Health Sciences and Professor of Medicine at Rutgers Robert Wood Johnson Medical School. Data from the study is expected in 4Q 2020.
Facts & FAQ’s
If EDP1815 is approved for COVID-19, Evelo could rapidly scale its manufacturing to supply the drug at a reasonable cost.
If the Phase 2/3 data are positive, Evelo will begin discussions with global regulatory agencies to determine if the data support registration. Additionally, if EDP1815 is approved for the treatment of COVID-19, Evelo could rapidly scale its manufacturing to supply the drug at a reasonable cost.
In the second and third quarter of 2019, Evelo reported positive Phase 1b interim clinical data in two cohorts of individuals with mild to moderate psoriasis. EDP1815 was well tolerated at both doses, with no overall difference reported from placebo. In a Phase 1b clinical study in psoriasis, EDP1815 was observed to blunt the production of multiple inflammatory cytokines, including IL-6, IL-8, TNF, and IL-1, and was well tolerated with no overall difference from placebo.
In preclinical models, EDP1815 has been observed to have effects on Th1, Th2, and Th17 pathways, including TNF, IL-4, IL-5, IL-6, IL-12p40, IL-13, and IL-17. Several of these cytokines have been implicated in the cytokine storm associated with severe complications of COVID-19. In these models, no activity was observed on type 1 interferons, which are important for anti-viral responses.
Inflammation has many triggers, but the processes and mediators are common. The importance of EDP1815’s biomarker results, in conjunction with the clinical responses in psoriasis patients, is that it shows modification of general systemic inflammation as well as localized inflammation in the skin of people with psoriasis. Therefore, EDP1815 may also have the potential to treat the disseminated inflammation that can lead to morbidity and mortality in viral diseases.
“A therapy that modulates multiple pathways and returns the immune system back to a state of stability could offer significant clinical benefit to patients with COVID-19. EDP1815 has the potential to help large numbers of COVID-19 patients across the globe as soon as they enter the hospital and before severe respiratory complications emerge, potentially alleviating the need for ventilators and ICU beds.”