Microbiome Report for Week Ending 2/2/19

Azitra Completes Enrollment in Clinical Trial of Topical Commensal Microbiological Agent
Azitra, Inc., a company developing microbiome-based cosmetics and therapeutics to treat skin diseases and conditions, announced on 1/30/19  that enrollment has been completed for the first human safety study of AZT-04. AZT-04 is the Company’s lead product candidate and is in development for cosmetic use and select therapeutic indications.

A balanced microbiome is critical to maintaining natural and healthy looking skin. AZT-04 is a formulated topical product that contains a proprietary strain of Staphyloccocus epidermidis (SE). SE is a natural commensal organism that lives on the skin of humans that has demonstrated the potential to improve skin appearance. The development of AZT-04 is based on extensive research supported by a large number of scientific publications showing the promise of SE to improve the appearance of the skin.

“There is growing scientific evidence that applying a SE commensal such as AZT-04 to the skin may have promise in remediation of different skin conditions,” said Julia Oh, Ph.D., Assistant Professor at The Jackson Laboratory. “This study is an important first step toward validating this concept, and gaining a better understanding of how AZT-04 performs.” The Jackson Laboratory and Azitra have a research collaboration, and Dr. Oh is a scientific advisor to the company.

Azitra’s first human study of AZT-04 is a cosmetic study and it will examine the safety of three doses as well as evaluate changes in the skin microbiome after topical application of the natural microbiological agent. This trial will be conducted as a double-blind, placebo-controlled study. The NCT number assigned by clinicaltrials.gov for this study is NCT03820076. In future studies, Azitra also plans to assess the potential of AZT-04 to prevent and treat rashes associated with cancer therapy, such as EGFR inhibitor-associated rashes.

4D Pharma Publishes Mechanistic Data on Live Biotherapeutic Immuno-Oncology Candidate
4D pharma plc (AIM: DDDD), a pharmaceutical company leading the development of Live Biotherapeutics, announced on 1/29/19 the publication of a paper outlining the mechanism and strong immuno-stimulatory effects of MRx0518.

The paper ‘The flagellin of candidate live biotherapeutic Enterococcus gallinarum MRx0518 is a potent immunostimulant’ (Lauté-Caly et al) is published in the Nature Publishing Group journal Scientific Reports.
4D researchers demonstrated that MRx0518 stimulates both the innate and adaptive immune systems and identified the bacterial flagellin (a specific component of the MRx0518 bacterium) that interacts with the host TLR5 receptors as a mediator of this process. The TLR5 pathway is known to be associated with the body’s response to cancer.

Dr Alex Stevenson, 4D’s Chief Scientific Officer, commented:
“This publication exemplifies our commitment to conducting leading microbiome research and further highlights the importance of a strain-level understanding of function and mechanism in selecting live biotherapeutic candidates for clinical development.”

4D is conducting a number of clinical trials with MRx0518 across a range of settings in 2019. The first of which, a combination study with Keytruda® in collaboration with Merck & Co., Inc., Kenilworth, NJ., USA, and conducted at MD Anderson Cancer Centre, is open for recruitment.

Evelo Biosciences Doses First Patient in Ph IIa Clinical Trial of EDP1503 in Combination with Keytruda in Patients with Metastatic Melanoma
Evelo Biosciences, Inc. (Nasdaq: EVLO) (“Evelo”) announced on 1/28/19 that the University of Chicago has dosed the first patient in an investigator-sponsored Phase 2a clinical trial evaluating EDP1503 in combination with Keytruda (pembrolizumab), Merck’s anti-PD-1 therapy. EDP1503 is an orally delivered monoclonal microbial product candidate being developed for the treatment of cancer.

This open-label clinical trial, led by Dr. Jason J. Luke, M.D., FACP, will evaluate the safety, tolerability, and efficacy of EDP1503 in combination with Keytruda in up to 70 patients with metastatic melanoma who are previously untreated or who have relapsed following treatment with an anti-PD-1 inhibitor. Evelo will provide and retain all rights to EDP1503.

Patients will receive daily EDP1503 monotherapy for two weeks followed by treatment with daily EDP1503 in combination with Keytruda. The study will evaluate biomarkers identified from paired biopsies taken before and after the two-week run-in, as well as clinical outcomes observed over the course of the trial, and potential alterations to the intestinal microbiome. Evelo anticipates initial clinical data from the trial in the second half of 2020.
In preclinical studies orally delivered EDP1503 shows activation of multiple clinically validated systemic immune pathways which are complementary to and potentially synergistic with checkpoint inhibitors. Effects include increased CXCL9 and CXCL10 production in the tumor microenvironment, augmentation of NK and T cell infiltration to the tumor site as well as upregulation of MHC Class I expression in tumors.

SkinBio Therapeutics Provides Update on Studies and IP Portfolio
SkinBioTherapeutics plc (AIM: SBTX – “SkinBioTherapeutics” or the “Company”), on 1/31/19 provided interim data on the third and final phase of its human studies and an update on one of its patents.

SkinBioTherapeutics has completed testing on 60 of the total 120 volunteers for its human study, with no compliance or safety concerns.The final 60 volunteers are now being treated and the Company remains on track to complete the study during Q1 2019 as expected.

The study is double-blinded, meaning neither the volunteers nor the experimenters know who is receiving a particular treatment, to prevent any bias. For this reason, SkinBioTherapeutics will need the full dataset before it can be ‘unblinded’ for statistical analysis. The data will then be assessed to determine effectiveness - whether theSkinBiotix® technology retains the same beneficial property of improving skin health when in a cream formulation.

The resulting safety, irritancy and effectiveness data will be shared with potential global partners interested in commercialising the SkinBiotix® technology. A number of these companies have provided input into the study testing and analysis protocols.

In addition to the interim human study data, the Company has expanded its patent portfolio, with a patent proceeding to grant in Mexico. Adding protection around the SkinBiotix® technology is a key part of the Company's strategy. This patent will add to those already granted in Australia, New Zealand and Russia and a number of other patent applications are in process.