30 Oct Non-Absorbable Microbe Has Potential To Reduce Inflammatory Disorders Including Psoriasis
MedicalResearch.com Interview with:
Dr. Douglas Maslin, MPhil, MB BCHir
Dermatologist and Pharmacologist
MedicalResearch.com: What is the background for this study?
Response: I’d like to answer this question in three parts:
Firstly, the background to Evelo and the therapeutic EDP1815: Evelo is developing orally administered biologic medicines based on a new understanding of how systemic inflammation is controlled. Evelo’s medicines are selected for their ability to modulate the small intestinal axis, or SINTAX, a network of anatomical and functional connections that has evolved to connect the small intestine with the rest of the body. SINTAX links small intestinal mucosal immunology with systemic inflammation and is now accessible with oral medicines. This inflammatory control pathway may enable a new class of products which are effective, safe, and can be manufactured affordably at large scale.
EDP1815 is a non-live pharmaceutical preparation of a strain of the bacterium Prevotella histicola isolated from the duodenum of a human donor. Its pharmacodynamic effect is through interactions with the immune cells within the small intestine and it has no systemic absorption. These local interactions in the small intestine then downregulate systemic inflammation. In fact, the inflammatory control afforded by targeting the small intestinal axis appears to result in the coordinated downregulation of multiple inflammatory pathways without immunosuppression, mimicking the body’s normal physiological processes of inflammation resolution.
Secondly, there is the key and exciting background pre-clinical data on EDP1815 – the details of which have been published today at the EADV conference. For example, oral administration of EDP1815 to mice has been shown to lead to striking therapeutic effects in in vivo models of delayed-type hypersensitivity, imiquimod-induced skin inflammation, fluorescein isothiocyanate cutaneous hypersensitivity, collagen-induced arthritis, and experimental acute encephalomyelitis (EAE).
The consistency of effect and dose shows that EDP1815 can coordinately resolve systemic inflammation across TH1, TH2 and TH17 pathways. This suggests the potential for clinical benefit across multiple diseases.
And, thirdly, there is the clinical unmet need for an oral, safe, effective treatment specifically for mild and moderate psoriasis patients, who have very limited treatment options outside of the poorly tolerated topical therapies, and these patients are reported to be dissatisfied with treatment options and therefore are often under-treated.
These three points explain the background to EDP1815 and the reason for progressing forward into the phase 1b in psoriasis.
MedicalResearch.com: What are the main findings? Might this work for other inflammatory disorders ie atopic dermatitis?
Response: Firstly, in terms of the phase 1b study: at the EADV conference I report that EDP1815 was evaluated in 2 dose cohorts of 12 and 18 patients with mild to moderate psoriasis randomized 2:1 active:placebo. Doses were 1.6×1011 bacterial cells (cohort L) and 8.0×1011 cells (cohort H) of freeze-dried powder in enteric capsules for 28 days, with follow-up off drug through 42 days.
EDP1815 was well tolerated at daily doses of up to 8.0×1011 cells administered for up to 28 days, with a tolerability and side-effect profile comparable to placebo. There were no serious adverse effects.
At day 28, the percentage reduction in PASI for both EDP1815 cohorts was 16%, compared to 1% for placebo. At day 42, the percentage improvement from baseline increased to 21% in the high dose cohort, but not in the low dose cohort (10%) or placebo cohorts (3%). The percentage reduction in LSS scores at 28 days were 15% (cohort H) and 23% (cohort L) , compared to a 1% increase from baseline in the placebo group.
These results provide proof of concept of the efficacy of EDP1815 in mild and moderate psoriasis, and alongside the safety data, were the catalyst for progression into the phase 2 study which is now underway in the UK, Poland, Hungary and the US, with interim results expected in mid-2021.
Finally, in terms of the second part of your question: yes, there is potential in other inflammatory diseases. The pre-clinical data discussed above show that EDP1815 is able to broadly resolve inflammation across a range of inflammatory pathways – including not only the Th17 inflammation that predominates in psoriasis. This has been the reason to progress EDP1815 in other inflammatory diseases, and is one of the other very exciting potential benefits of a treatment engaging with SINTAX. In fact, the pre-clinical data in models of allergic inflammation see clinical efficacy of EDP1815 that is comparable to antibody and JAK inhibitor treatments. Because of this, we have progressed EDP1815 into a phase 1b clinical trial in mild and moderate atopic dermatitis which has now fully recruited, with the results expected in the first quarter of 2021.
In addition, two clinical trials for EDP1815 as a therapeutic treatment in patients hospitalised with COVID-19 are underway, including a UK national platform study sponsored by Addenbrooke’s hospital in the UK.
MedicalResearch.com: What should readers take away from your report?
Response: I would like readers to read my report or watch my talk, and leave feeling excited by the potential for a new oral, safe, and affordable therapy with potential to help a vast number of patients.
This is a potential therapy with a previously unexplored mechanism of action, that changes our understanding of immune system control. In fact, the mechanism allows for broad inflammation resolution, without immunosuppression, and so has potential across a wide spectrum of inflammatory diseases, including mild-moderate psoriasis.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: EDP1815 has now entered a large multi-national phase 2 dose-ranging study of 225 patients with mild to moderate psoriasis. Based on these results, it will be progressed forward into phase 3 studies before hopefully becoming available as a therapy for patients which could change the psoriasis standard of care.
With the results of this phase 2 study, and the phase 1 study in atopic dermatitis, future indications will be considered for the anti-inflammatory actions of EDP1815.
Finally, as this study, combined with an immunopharmacology study in healthy volunteers, have validated the approach of targeting SINTAX, Evelo have expanded their platform and will soon initiate a trial with another host commensal microbe, EDP1867.
MedicalResearch.com: Is there anything else you would like to add?
Response: Thank you for the interview.
My disclosures are that I work for Evelo Biosciences as their clinical lead in immunology.
SAFETY AND EFFICACY OF AN ORALLY ADMINISTERED, SINGLE STRAIN COMMENSAL MICROBE IN PSORIASIS AFTER 28 DAYS OF THERAPY: EDP1815
29th European Academy of Dermatology and Venereology Congress
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