Itano Andrea, Maslin Douglas, Ramani Kritika, Mehraei Golbarg, Carpenter Nancy, Cormack Taylor, Saghari Mahdi, Moerland Matthijs, Troy Erin, Caffry Will, Wardwell-Scott Leslie, Abel Stuart, McHale Duncan, Bodmer Mark
Evelo Biosciences, Cambridge, MA, United States.
Centre for Human Drug Research (CHDR), Leiden, Netherlands.
Front Med (Lausanne). 2023 May 5;10:1070433. doi: 10.3389/fmed.2023.1070433. eCollection 2023.
EDP1815 is a non-colonizing pharmaceutical preparation of a single stain of 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.
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.
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.
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.: EudraCT # 2018-002807-32; EudraCT # 2018-002807-32; NL8676; https://clinicaltrials.gov/ct2/show/NCT03733353; http://www.trialregister.nl.
EDP1815是一种从人类供体十二指肠分离出的单一菌株的非定植性药物制剂。我们在此报告临床前和临床研究，表明EDP1815这种口服给药且局限于肠道的单一共生细菌菌株的作用可调节全身的炎症反应。
在三种Th1、Th2和Th17介导的炎症的临床前小鼠模型中，EDP1815具有抗炎活性的证据支持下，在三项1b期研究中对其进行了临床测试，分别针对银屑病患者、特应性皮炎患者以及在KLH皮肤激发模型中的健康志愿者。
在临床前，EDP1815在所有三种炎症小鼠模型中均有效，显示出皮肤炎症以及相关组织细胞因子的减少。在1b期研究中，发现参与者对EDP1815耐受性良好，安全性与安慰剂相当，包括未报告严重或持续的副作用，且在这些研究中没有免疫抑制的证据，也没有机会性感染发生。在银屑病患者中，治疗4周后出现临床疗效迹象，在高剂量组中治疗期结束后仍持续存在。在特应性皮炎患者中，在关键的医生和患者报告的结局方面均有改善。在一项关于KLH诱导的皮肤炎症反应的健康志愿者研究中，通过基于成像的皮肤炎症测量方法，在两个队列中均观察到一致的抗炎作用。
这是第一份证明用非定植性肠道局限单一共生细菌菌株靶向外周炎症产生临床效果的报告，为一类新型药物提供了概念验证。这些临床效果在没有EDP1815全身暴露或常驻肠道微生物群改变的情况下出现，且具有类似安慰剂的安全性和耐受性。EDP1815这些临床效果的广度，再加上其出色的安全性和耐受性以及口服给药方式，表明有可能出现一种新型的有效、安全、口服且易于获得的抗炎药物，用于治疗由炎症驱动的广泛疾病。：欧盟临床试验注册号#2018-002807-32；欧盟临床试验注册号#2018-002807-32；荷兰试验注册号NL8676；https://clinicaltrials.gov/ct2/show/NCT03733353；http://www.trialregister.nl。
