LUGANO, Switzerland—The European Academy of Dermatology and Venereology’s (EADV) 29th Congress, EADV Virtual, was held Oct. 29-31 and launched on World Psoriasis Day. The event featured some of the latest research into dermatological conditions, and among the presenters was Evelo Biosciences, which shared data from its Phase 1b clinical study of EDP1815.
EDP1815 is a preparation of a non-living, single strain of the bacterium Prevotella histicola, isolated from the duodenum (small intestine) of a human donor. This investigational therapy is orally administered, and is being developed to treat inflammatory diseases. The Phase 1b study assessed EDP1815 in two cohorts of 12 and 18 patients with mild-to-moderate psoriasis for 28 days, with follow-up off treatment through 42 days.
Data so far demonstrate that EDP1815 was well tolerated at daily doses of up to 8.0x101 cells administered for up to 28 days, with a tolerability profile comparable to placebo. At day 28, the mean percentage reduction in participants’ Psoriasis Area Severity Index (PASI) score for both cohorts was 16 percent, compared to 1 percent for placebo. The higher dose cohort saw additional improvement for a 21-percent mean percentage reduction at 42 days, but the low-dose cohort reported results of 10 percent while the placebo group reported 3 percent. Mean reduction in Lesion Severity Scores (LSS) at 28 days were 15 percent and 23 percent in the high- and low-dose cohorts, respectively, while the placebo group saw a 1-percent increase from baseline. The high-dose group improved to a 24-percent reduction.
“Although several treatments options are available for psoriasis patients with the most severe disease, there is a great need for new innovative methods for those living with mild-moderate disease,” said Dr. Douglas Maslin, dermatologist and pharmacologist at Addenbrooke’s Hospital in Cambridge, U.K. “I decided to work with Evelo Biosciences after seeing the huge potential in EDP1815 and its oral mechanism of action. It is a real breakthrough, especially as we have seen from the preclinical and Phase 1 trials that it was well tolerated with no overall difference from placebo and with no severe side effects reported. We are extremely encouraged to see that these data support further clinical development of EDP1815 in psoriasis. We are already in Phase 2 clinical trials across the U.K., Poland and U.S. This is a potentially massive win for the majority of psoriasis patients, as it has the potential to improve treatment options and perhaps change the current standard of care.”
Maslin, who is working on secondment with Evelo Biosciences, led the Phase 1b clinical study.
Psoriasis is a chronic inflammatory skin disease characterized by raised plaques and scales on the surface of the skin, and approximately 2 to 3 percent of all adults are affected by psoriasis globally. The most common type is plaque psoriasis, which presents in 80 percent of psoriatic individuals. Evelo reported in a corporate presentation that its “initial commercial focus is on mild-to-moderate population, with potential to address over 3.5 million of these individuals in U.S. and EU5 [France, Germany, Italy, Spain and the U.K.] and then expand globally.”
EDP1815 acts upon the small intestinal axis, which is a network of connections bridging the small intestine and the rest of the body. The therapy triggers systemic therapeutic effects without likewise causing systemic absorption or modification of the microbiome. Within the small intestine, epithelial and dendritic cells regularly sample the contents of the lumen, and when they encounter EDP1815, the cells modulate inflammation via cytokine signaling and T cell trafficking. In preclinical mouse models, EDP1815 administration led to significant reductions in Th1, Th2 and Th17 inflammation.
Evelo will be moving EDP1815 into Phase 2 development in mild-to-moderate psoriasis, which will consist of a double-blind, placebo-controlled, dose-ranging trial that will enroll approximately 225 patients, including participants with more active disease scores than those enrolled in the Phase 1b trial. The trial will evaluate three doses of EDP1815 vs. placebo, and the primary endpoint will be a mean reduction in PASI scores at 16 weeks.
The company noted in a corporate presentation in October that it was also advancing EDP1815 in a Phase 1b study in atopic dermatitis. EDP1867, another pipeline candidate, will be the focus of a Phase 1b trial in atopic dermatitis as well, with an expected trial initiation date in Q1 2021. Data from the Phase 1b trial of EDP1815 in atopic dermatitis is expected in Q1 2021, and interim data from the Phase 2 trial of EDP1815 in psoriasis is expected by mid-2021.
“Although there are many effective biologics, they are not suitable for all patients with psoriasis,” remarked Associate Professor Eniko Sonkoly from the Department of Medicine for the Karolinska Institute and Karolinska University Hospital Solna in Sweden. Sonkoly presented on the current small-molecule pipeline for psoriasis at EADV Virtual. “There is a need for new oral and topical treatments with favorable safety profiles that can benefit mild, moderate and severe patients, improving their quality of life. Small molecules have the advantage of being suitable for both oral and topical delivery and have the potential to improve available treatment options.”