This is an Open-Label Extension (OLE) study to evaluate the long-term safety, tolerability, and efficacy of EDP1815 in participants with mild, moderate, and severe atopic dermatitis who have completed the treatment period of a prior clinical study ("parent study") with EDP1815.
The current parent study of this protocol is the EDP1815-207 study; A Phase 2, Multicenter, Double-Blind, Placebo-Controlled, Multiple-Cohort Study Investigating the Effect of EDP1815 in Participants for the Treatment of Mild, Moderate and Severe Atopic Dermatitis.

Start Date06 Jun 2022

Sponsor / Collaborator

Evelo Biosciences, Inc.

NCT05121480

/ CompletedPhase 2

A Phase 2, Multicenter, Double-Blind, Placebo-Controlled, Multiple-Cohort Study Investigating the Effect of EDP1815 in Participants for the Treatment of Mild, Moderate and Severe Atopic Dermatitis

The purpose of this research study is to determine whether the study drug, EDP1815, is safe and effective in the treatment of atopic dermatitis compared with placebo. The study will look at different doses of the study drug, and whether there are differences when the drug is given once daily or twice daily.

Start Date31 Jan 2022

Sponsor / Collaborator

Evelo Biosciences, Inc.

100 Clinical Results associated with EDP-1815

100 Translational Medicine associated with EDP-1815

100 Patents (Medical) associated with EDP-1815

Literatures (Medical) associated with EDP-1815

01 Aug 2024·IMMUNOLOGIC RESEARCH

Immunomodulating effects of the single bacterial strain therapy EDP1815 on innate and adaptive immune challenge responses — a randomized, placebo-controlled clinical trial

Article

Author: In 't Veld, Aliede E ; Moerland, Matthijs ; Jansen, Manon A A ; Itano, Andrea ; Eveleens Maarse, Boukje C ; Niemeyer-van der Kolk, Tessa ; McHale, Duncan ; Ronner, Micha N ; Ahmad, Saira ; Klaassen, Erica S

Abstract:

The gut microbiome can modulate systemic inflammation and is therefore target for immunomodulation. Immunomodulating effects of EDP1815, a bacterial commensal strain of Prevotella histicola, were studied in healthy participants. Effects on adaptive immunity were evaluated by a neo-antigen challenge with keyhole limpet haemocyanin (KLH), while effects on innate immunity were evaluated by topical toll-like receptor 7 (TLR7) agonist imiquimod. Capsules with two enteric coating levels (EC1, EC2) were compared. Thirty-six healthy participants were included and received a daily dose of 8 × 1010 cells EDP1815-EC1, EDP1815-EC2 or placebo (randomization 1:1:1) for 60 days. They received KLH vaccinations at days 8, 24 and 36, with intradermal skin challenge at day 57. KLH challenge outcomes were antibody levels, and skin blood flow and erythema after skin challenge, measured by imaging techniques. Imiquimod administration started at day 57, for 72 h. Outcomes consisted of imaging measurements similar to the KLH challenge, and the influx of inflammatory cells and cytokines in blister fluid. There was no effect of EDP1815 treatment on the KLH challenge, neither on the imaging outcomes of the imiquimod challenge. There was a consistently lower influx of inflammatory cells in the blister fluid of EDP1815-treated participants (neutrophils, p = 0.016; granulocytes, p = 0.024), more pronounced in EC1. There was a lower influx of interleukin [IL]-1β, IL-6, IL-8, IL-10, interferon [IFN]-γ and tumour necrosis factor in blister fluid of EDP1815-treated participants. EDP1815 had immunomodulatory effects on the innate immune response driven by imiquimod, but no effect on the KLH challenge was observed. Trial registration number: NCT05682222; date: 22 July 2022.

Frontiers in medicine

Clinical translation of anti-inflammatory effects of Prevotella histicola in Th1, Th2, and Th17 inflammation

Article

Author: Duncan McHale ; Mahdi Saghari ; Stuart Abel ; Will Caffry ; Kritika Ramani ; Douglas Maslin ; Matthijs Moerland ; Nancy Carpenter ; Golbarg Mehraei ; Leslie Wardwell-Scott ; Mark Bodmer ; Andrea Itano ; Taylor Cormack ; Erin Troy

Introduction:

EDP1815 is a non-colonizing pharmaceutical preparation of a single stain of Prevotella histicola isolated from the duodenum of a human donor. We report here preclinical and clinical studies showing that the action of EDP1815, an orally delivered and gut restricted single strain of commensal bacteria can regulate inflammatory responses throughout the body.

Methods:

Supported by evidence for anti-inflammatory activity in three preclinical mouse models of Th1-, TH2-, and Th17-mediated inflammation, EDP1815 was tested clinically in three Phase 1b studies in patients with psoriasis, patients with atopic dermatitis, and healthy volunteers in a KLH skin challenge model.

Results:

Preclinically, EDP1815 was efficacious in all three mouse models of inflammation, showing reduction in skin inflammation as well as related tissue cytokines. In the Phase 1b studies, EDP1815 was found to be well tolerated by participants, with a safety profile comparable to placebo, including no severe or consistent side-effects reported, and no evidence of immunosuppression with no opportunistic infection occurring in these studies. In psoriasis patients, signs of clinical efficacy were seen after 4 weeks of treatment, which continued beyond the treatment period in the higher-dose cohort. In atopic dermatitis patients, improvements were seen throughout the key physician-and patient-reported outcomes. In a healthy-volunteer study of a KLH-induced skin inflammatory response, consistent anti-inflammatory effects were seen in two cohorts through imaging-based measures of skin inflammation.

Discussion:

This is the first report demonstrating clinical effects from targeting peripheral inflammation with a non-colonizing gut-restricted single strain of commensal bacteria, providing proof of concept for a new class of medicines. These clinical effects occur without systemic exposure of EDP1815 or modification of the resident gut microbiota, and with placebo-like safety and tolerability. The breadth of these clinical effects of EDP1815, combined with its excellent safety and tolerability profile and oral administration, suggests the potential for a new type of effective, safe, oral, and accessible anti-inflammatory medicine to treat the wide range of diseases driven by inflammation.Clinical Trial Registration: EudraCT # 2018-002807-32; EudraCT # 2018-002807-32; NL8676; https://clinicaltrials.gov/ct2/show/NCT03733353; http://www.trialregister.nl.

01 Dec 2020·Trials

muLTi-Arm Therapeutic study in pre-ICu patients admitted with Covid-19-Experimental drugs and mechanisms (TACTIC-E): A structured summary of a study protocol for a randomized controlled trial

Letter

Author: Bond, Simon ; Norton, Sam ; Galloway, James ; Kulkarni, Spoorthy ; Fisk, Marie ; Lu, Ing Ni ; Hall, Frances ; Cheriyan, Joseph ; Jayne, David ; Cope, Andrew ; Kostapanos, Michalis ; Wilkinson, Ian B ; Kadyan, Sonakshi ; Banham-Hall, Edward

Abstract:

Objectives:

To determine if a specific intervention reduces the composite of progression of patients with COVID-19-related disease to organ failure or death as measured by time to incidence of any one of the following: death, invasive mechanical ventilation, ECMO, cardiovascular organ support (inotropes or balloon pump), or renal failure (estimated Cockcroft Gault creatinine clearance <15ml/min).

Trial design:

Randomised, parallel arm, open-label, adaptive platform Phase 2/3 trial of potential disease modifying therapies in patients with late stage 1/stage 2 COVID-19-related disease, with a diagnosis based either on a positive assay or high suspicion of COVID-19 infection by clinical, laboratory and radiological assessment.

Participants:

Patients aged 18 and over, with a clinical picture strongly suggestive of COVID-19-related disease (with/without a positive COVID-19 test) AND a risk count (as defined below) >3 OR ≥3 if risk count includes “Radiographic severity score >3”. A risk count is calculated by the following features on admission (1 point for each): radiographic severity score >3, male gender, non-white ethnicity, diabetes, hypertension, neutrophils >8.0 x109/L, age >40 years and CRP >40 mg/L.Patients should be considered an appropriate subject for intervention with immunomodulatory or other disease modifying agents in the opinion of the investigator and are able to swallow capsules or tablets. The complete inclusion and exclusion criteria as detailed in the Additional file 1 should be fulfilled. Drug specific inclusion and exclusion criteria will also be applied to the active arms. Patients will be enrolled prior to the need for invasive mechanical ventilation, cardiac or renal support. Participants will be recruited across multiple centres in the UK including initially at Cambridge University Hospitals NHS Foundation Trust and St George’s University NHS Foundation Trust. Other centres will be approached internationally in view of the evolving pandemic.

Intervention and comparator:

There is increasing evidence of the role of immunomodulation in altering the course of COVID-19. Additionally, various groups have demonstrated the presence of pulmonary shunting in patients with COVID-19 as well as other cardiovascular complications. TACTIC-E will assess the efficacy of the novel immunomodulatory agent EDP1815 versus the approved cardio-pulmonary drugs, Dapagliflozin in combination with Ambrisentan versus the prevailing standard of care.EDP1815 will be given as 2 capsules twice daily (1.6 x 1011 cells) for up to 7 days with the option to extend up to 14 days at the discretion of the principal investigator or their delegate, if the patient is felt to be clinically responding to treatment, is tolerating treatment, and is judged to be likely to benefit from a longer treatment course. Ambrisentan 5mg and Dapagliflozin 10mg will be given in combination once daily orally for up to maximum of 14 days. Patients will be randomised in a 1:1:1 ratio across treatments. Each active arm will be compared with standard of care alone. Additional arms may be added as the trial progresses. No comparisons will be made between active arms in this platform trial.

Main outcomes:

The primary outcome is the incidence (from baseline up to Day 14) to the occurrence of the any one of the following events: death, invasive mechanical ventilation, extra corporeal membrane oxygenation, cardiovascular organ support (inotropes or balloon pump), or renal failure (estimated Cockcroft Gault creatinine clearance <15ml/min).

Randomisation:

Eligible patients will be randomised using a central web-based randomisation service (Sealed Envelope) in a 1:1:1 ratio, stratified by site to one of the treatment arms or standard of care.

Blinding (masking):

This is an open-label trial. Data analysis will not be blinded.

Numbers to be randomised (sample size):

There is no fixed sample size for this study. There will be an early biomarker-based futility analysis performed at a point during the study. If this biomarker futility analysis is not conclusive, then a second futility analysis based on clinical endpoints will be performed after approximately 125 patients have been recruited per arm. Provisionally, further analyses of clinical endpoints will be performed after 229 patients per active arm and later 469 patients per arm have been recruited. Further additional analyses may be triggered by the independent data monitoring committee.

Trial Status:

TACTIC-E Protocol version number 1.0 date May 27th, 2020. Recruitment starts on the 3rd of July 2020. The end trial date will be 18 months after the last patient’s last visit and cannot be accurately predicted at this time.

Trial registration:

Registered on EU Clinical Trials Register EudraCT Number: 2020-002229-27 registered: 9 June 2020.The trial was also registered on ClinicalTrials.gov (NCT04393246) on 19 May 2020.

Full protocol:

The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

News (Medical) associated with EDP-1815

22 Nov 2023

·medcitynews.com

Evelo Bio Shutdown Follows a Series of Microbiome Therapy Trial Failures

Evelo Biosciences is shutting down, a move that follows a series of clinical trial setbacks, a corporate downsizing, and the failure to secure additional financing to continue its work developing microbiome therapies that work in the gut to treat immune disorders. Cambridge, Massachusetts-based Evelo disclosed the dissolution plans in a Tuesday regulatory filing. The company said that on Monday, the board of directors determined that dissolving the business is in the best interests of Evelo and its stockholders. “The board believes dissolution presents the best opportunity for recovery for the company’s creditors and may also provide an opportunity for future payments to its other stakeholders, including Evelo’s stockholders,” the company said in the filing. Evelo was formed in 2014 by investment firm and startup creator Flagship Pioneering. Incubating within Flagship’s VentureLabs, the company researched the interface between microbes and the immune system. Evelo went on to develop orally administered microbes intended to engage with the gut to drive immune responses for the potential treatment of inflammatory conditions and cancer. When the company went public in a 2018 IPO that raised $85 million, its most advanced programs were in early clinical development in atopic dermatitis and psoriasis. Evelo’s microbiome therapies failed to live up to their promise in the clinic. The company weathered disappointing data readouts for various microbiome therapeutic candidates. The clinical trial setbacks continued into this year. In February, Evelo announced results for EDP1815 in atopic dermatitis showing that the first three cohorts in a Phase 2 test did not meet the main study goal. Citing the challenging financial environment, Evelo implemented cost-cutting measures, including layoffs. In April, Evelo reported that the fourth cohort of EDP1815’s Phase 2 test, which evaluated a faster-release formulation, also missed the trial goal. Consequently, Evelo discontinued further development of this atopic dermatitis candidate. Evelo’s annual report issued in March listed a cash position of $47.9 million, which the company estimated would be enough to last only into the third quarter of this year. In July, the company closed a $25.5 private placement led by Flagship, which the company planned to use to complete Phase 2a testing of EDP2939 as a treatment for moderate psoriasis. But last month, Evelo announced that this drug candidate also failed to meet the main clinical trial goal. The company announced the exploration of strategic alternatives, such as finding partners for its assets and the platform technology used to develop them. No deals were done. The field of microbiome therapies is making headway, but the progress has been hard won. Seres Therapeutics, a Flagship-founded company, won FDA approval in April for Vowst, a capsule containing live microbes intended to restore equilibrium to the gut microbiome as a way of treating recurrent Clostridioides difficile infection. The landmark regulatory decision followed a Phase 2 clinical trial failure that set back Seres’s research for years. Kaleido Biosciences, yet another Flagship-founded microbiome biotech, shut down last year following its own clinical trial and financing misses. According to the Evelo regulatory filing, the company’s entire board resigned on Monday. CEO Simba Gill and CFO Marella Thorell have also lost their jobs. They will continue to consult with and advise the company on matters related to the dissolution for a fee of $3,150 per day for Gill and $2,262 for Thorell. Before the board resigned, it appointed Craig Jalbert to take over the duties of Gill and Thorell. Jalbert is a principal of accounting firm Verdolino & Lowey, and his experience includes overseeing the wind down of public and private companies. Evelo will pay Jalbert $10,000 per month until the company’s dissolution. The dissolution plan still needs the approval of Evelo shareholders. The date of the shareholder meeting has not yet been determined. Evelo’s opening stock price on Wednesday was 57 cents. When Evelo went public in 2018, it priced its shares at $16 apiece. Image: spawns, Getty Images

Phase 2Executive ChangeMicrobial therapyClinical Trial FailureIPO

22 Nov 2023

·www.fiercebiotech.com

Evelo's voyage ends as Flagship-founded biotech finds dissolution is only viable option

Evelo Biosciences has tasked Rock Creek Advisors with helping find deals for its assets. Evelo Biosciences is dissolving. One month after starting a search for strategic alternatives, the Flagship Ventures-backed microbiome biotech has found its only option is to close its doors and hand any cash to creditors. The biotech, which has suffered a series of setbacks over the past 18 months, outlined its plans in a Securities and Exchange Commission filing. After failing to find funding or other ways to keep going, the board identified the dissolution of the business as the only viable option. The board sees closing as Evelo’s best shot at paying its creditors and potentially returning some cash to shareholders. Simba Gill, Ph.D., and Marella Thorell, respectively the CEO and chief financial officer at Evelo, are leaving the company along with all seven members of the board. The pair survived the 45% reduction in head count that Evelo enacted in January along with further cuts it made in the second quarter. Craig Jalbert, an insolvency expert, will oversee the dissolution process. Evelo has tasked Rock Creek Advisors with helping identify strategic alternatives to help monetize its assets, which were once seen as highly promising. VC shops including Flagship, GV and Celgene anointed Evelo as a biotech with the potential to realize the therapeutic promise of the microbiome, committing cash across private rounds and propping up its $85 million IPO. Going into 2022, the biotech was testing its belief that orally administered microbial strains can up- or down-regulate immune pathways across studies of three drug candidates. All of the candidates disappointed. Work on EDP1867 stopped in April 2022 after it failed to impress in a phase 1 atopic dermatitis trial. Another atopic dermatitis candidate, EDP1815, flunked a phase 2 clinical trial early this year. The last asset left, EDP2939, recently performed worse than placebo in psoriasis. Evelo tapped Horizon Technology Finance Corp. for a $45 million loan to fund its pipeline through the data drops in 2023. Talking to investors in March, Horizon President Gerald Michaud cited Evelo’s platform technology and multiple clinical trials, plus Flagship’s support, as reasons to think the biotech could overcome the setback in atopic dermatitis. Horizon, like Flagship, moved to sell stock in August. The clinical development programs fell away one by one, leaving Evelo in June with a once-hyped platform that was tarnished by the flops as well as $7.6 million in cash and $43.9 million in debt. The biotech later added cash and reduced its debt but in the end was unable to secure its financial future.

IPOPhase 1Clinical Trial FailureFinancial StatementMicrobial therapy

22 Nov 2023

·firstwordpharma.com

End of the road for Evelo as no “viable alternative” found

Evelo Biosciences disclosed in a filing with the US Securities and Exchange Commission that it will dissolve the business after failing to find a “viable alternative.” The company began exploring its options last month after announcing the second setback this year for one of its experimental drugs.The most recent study failure involved EDP2939, which fared worse than placebo at alleviating psoriasis symptoms in a Phase II trial. Specifically, at the 16-week mark of the study, 19.6% of patients on EDP2939 versus 25% of those on placebo achieved the primary endpoint of at least a 50% improvement from baseline in Psoriasis Area and Severity Index (PASI 50).Earlier in the year, Evelo ended further development of EDP1815 in atopic dermatitis after winding down a Phase II study of the drug. In the trial, 37.9% of those on EDP1815 achieved the primary endpoint of at least a 50% improvement from baseline in Eczema Area and Severity Index (EASI) score, versus 44.7% in the placebo arm.Sought partnerShortly after the EDP2939 failure, Morgan Stanley analysts noted that Evelo was focused on finding a partner for EDP1815 and its small intestinal axis (SINTAX) platform before the end of 2023. However, they cautioned that the setback for EDP2939 would make it difficult for the company “to obtain a partnership with attractive economic terms in the near term.”Evelo said that the dissolution comes after it sought potential funding sources and other ways to continue to operate its business. The company – which was founded by Flagship Ventures in 2014 – suggested that winding down operations “presents the best opportunity for recovery for…creditors and may also provide an opportunity for future payments to its other stakeholders.”

Phase 2Clinical ResultClinical Trial Failure

100 Deals associated with EDP-1815

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
COVID-19	Phase 3	United Kingdom	Cambridge University Press	01 Jul 2020
Dermatitis, Atopic	Phase 2	United States	Evelo Biosciences, Inc.	06 Jun 2022
Dermatitis, Atopic	Phase 2	Australia	Evelo Biosciences, Inc.	06 Jun 2022
Dermatitis, Atopic	Phase 2	Bulgaria	Evelo Biosciences, Inc.	06 Jun 2022
Dermatitis, Atopic	Phase 2	Canada	Evelo Biosciences, Inc.	06 Jun 2022
Dermatitis, Atopic	Phase 2	Germany	Evelo Biosciences, Inc.	06 Jun 2022
Dermatitis, Atopic	Phase 2	Poland	Evelo Biosciences, Inc.	06 Jun 2022
Mild Atopic Dermatitis	Phase 2	United States	Evelo Biosciences, Inc.	31 Jan 2022
Mild Atopic Dermatitis	Phase 2	Australia	Evelo Biosciences, Inc.	31 Jan 2022
Mild Atopic Dermatitis	Phase 2	Bulgaria	Evelo Biosciences, Inc.	31 Jan 2022

Clinical Result

Indication

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04603027 (phase 2, Pubmed)	Phase 2	Plaque psoriasis	-	EDP1815 1 capsule	gwqxklkivd(zcyltqvwzr) = comparable rates of treatment-emergent adverse events to placebo, and no drug-related serious adverse events yhahrktgrb (tqdabqbyqw )	Positive	01 Jan 2024
				EDP1815 4 capsules
NCT05439941 (CTgov)	Phase 2	Dermatitis, Atopic	287	EDP1815 (Group 1)	zwdcaqstgd(qabkdnmdby) = uwncxapzay pcalnzjgsa (rrqyqzhjcx, ojajipvcts - wfbbzacshi) View more	-	07 Sep 2023
				EDP1815 (Group 2)	zwdcaqstgd(qabkdnmdby) = drzgppyqau pcalnzjgsa (rrqyqzhjcx, qhbqajgzfn - bktypittnn) View more
NCT05121480 (CTgov)	Phase 2	Moderate Atopic Dermatitis \| Mild Atopic Dermatitis \| Severe Atopic Dermatitis	421	Placebo (Cohorts 1-3 - Placebo)	cydrwxqkhz = xlevdbrmle sgkjboineo (qfvcbegzwj, ewktosyuyj - enpskjiqip) View more	-	16 Aug 2023
				EDP1815 (Cohort 1 - Active)	cydrwxqkhz = wmcgddcbgb sgkjboineo (qfvcbegzwj, rgrcppvhuh - oguupnspfx) View more
NCT04488575 (CTgov)	Phase 2	COVID-19	16	Placebo (Placebo)	lqucvqessu(umzzcuseyw) = wdantanqxt lmefmvekig (vdlwgkntny, 114.95) View more	-	19 Dec 2022
				EDP1815 (EDP1815)	lqucvqessu(umzzcuseyw) = omqpoxmgxb lmefmvekig (vdlwgkntny, 76.85) View more
NCT04603027 (phase 2 \| EDP1815-201, CTgov)	Phase 2	Plaque psoriasis	249	placebo (All Placebo)	rjdahndhtq(aafhkahomn) = tdikflhmpb qjphmhrhwq (fzolniuxmb, wnnnwkjxbl - tjqjheevjh) View more	-	19 Dec 2022
				EDP1815 (Cohort 1 Active)	rjdahndhtq(aafhkahomn) = ecokuwkrid qjphmhrhwq (fzolniuxmb, jibdkvgdla - fcxgehndtx) View more
NCT04603027 (EDP1815-201, EADV2022)	Phase 2	Psoriasis	249	EDP1815	ndudexksup(njncuafuco) = blejpvlmnw yysoihwjml (ckonnjqreh )	-	07 Sep 2022
				Placebo	ndudexksup(njncuafuco) = rdtgixpnor yysoihwjml (ckonnjqreh )
NCT04603027 (Corporate Publications) Manual	Phase 2	Psoriasis \| Systemic Inflammatory Response Syndrome	249	EDP1815	vpbzsdhiai(pedjagxfto) = zlojdurnox ljdhnuzfez (trazrydmcm ) View more	Positive	27 Sep 2021
				Placebo	sgsmknbuly(ratzipioqu) = ioythujynk xzzghydqdt (kmczpbdcxg )
NCT03733353 (GlobeNewswire) Manual	Phase 1	Dermatitis, Atopic	23	EDP1815	ptsjehngxc(yykdmaarot) = no serious adverse events. urufrnjoez (wwnhwippwq ) View more	Positive	09 Dec 2020
				Placebo

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