Being Tested in Combination with MSD’s anti-PD-1 Therapy, KEYTRUDA® (pembrolizumab)

Cambridge, UK – 7 October 2024: Microbiotica, a clinical-stage biopharma company developing a pipeline of oral precision microbiome medicines called live biotherapeutic products (LBPs), announces that the first patient has been dosed in its advanced melanoma (MELODY-1) trial. This international trial is due to recruit up to 40 patients at clinical centres in the UK, France, Italy and Spain. Initial data readouts are expected by the end of 2025.

Melanoma is a life-threatening skin cancer that can spread to other parts of the body in its advanced stages. PD-1 inhibitor immunotherapies have revolutionised cancer treatment and are now commonly used to treat melanoma. However new treatment options are still needed to extend the benefit to patients for whom immunotherapies do not work (treatment-resistant patients). This can be up to 50% of all advanced melanoma patients.

MB097 is a once daily, orally administered LBP consisting of a defined consortium of nine strains of commensal bacteria designed to enhance the efficacy of immune checkpoint inhibitors (ICIs). The MELODY-1 study will investigate the safety, tolerability, and initial signals of efficacy of MB097 in advanced (metastatic) melanoma, in combination with KEYTRUDA^® (pembrolizumab), MSD's (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy, in patients with cutaneous melanoma who have failed to respond to immunotherapies. MSD will supply KEYTRUDA (study identifiers NCT06540391; MSD KEYNOTE-E75; 023-507377-17).

This is a Phase 1b, first-in-human, randomised open-label clinical trial with all patients receiving MB097 and pembrolizumab for up to six months. Half of the participants will also receive vancomycin before starting the co-therapy to determine whether it helps the bacterial strains in MB097 embed and grow in the gut more efficiently. Participants benefiting from the treatment at the end of the initial six-month period may continue to receive pembrolizumab for up to an additional 18 months (approximately 24 months total). There will be up to 18 sites taking part in the study across the four countries.

As well as assessing the safety and tolerability of the co-therapy, the trial will measure standard oncology treatment efficacy including imaging measurements of tumour response. In addition, it will measure the engraftment of the strains being dosed, and changes in several immune biomarkers.

The bacterial strains in MB097 were identified by analysing the microbiome of patients in multiple studies of ICIs in melanoma, including the MELRESIST study carried out with the company’s collaborators at Cambridge University Hospitals, UK. Collectively, the MB097 bacterial consortium provides microbiome signalling that appears to be needed for ICI response. Pre-clinical studies demonstrate that MB097 activates core pathways of the immune system including Cytotoxic T Lymphocytes and Natural Killer cells to enable them to kill tumour cells. Research to understand the mechanism of action of the nine bacterial strains has indicated that in addition to this immune-activating effect, the bacteria in MB097 produce metabolites that act directly at the site of the tumour.

Ron Carter, Microbiotica’s Chief Medical Officer, said, “The gut microbiome, the community of bacteria in the gut, plays a crucial role in digesting food and protecting people from infections, but it also interacts very closely with the immune system. In cancer patients, the bacteria in MB097 appear to be associated with better response rates to immune checkpoint inhibitor therapies, such as anti PD-1 drugs. MB097, with its precisely selected microbes based on data from responsive patients, in combination with ICIs, could therefore activate a therapeutic benefit for non-responding patients with advanced melanoma. Moreover, as the MB097 bacteria are found in healthy subjects as well as in patients who responded to ICIs, we anticipate a favourable safety profile.”

Professor Paolo A. Ascierto, Director of the Unit of Melanoma, Cancer Immunotherapy and Development Therapeutics, National Tumor Institute Fondazione G. Pascale, Naples, Italy where the first patient has been dosed said, “Combining beneficial microbes with immune checkpoint inhibitors to increase the number of patients who could benefit from these life-saving therapies is a cutting-edge modality that could change the medical paradigm for advanced melanoma patients. With more than half of patients with melanoma being treated with anti PD-1 drugs either not responding or relapsing, I have great hope that the addition of a MB097 precision microbiome therapy such to the treatment regime can improve the outcome for many more patients.”

Pippa Corrie, PhD, FRCP, Affiliated Associate Professor of Medical Oncology, University of Cambridge, leading the UK arm of the study, said, “Our MELRESIST study has been fundamental in identifying precisely those gut bacteria that are associated with positive outcomes for melanoma patients on ICIs. The microbial signature comprising a small group of bacteria that were consistently raised in abundance in responding patients across multiple independent cohorts, which gives confidence that MB097 has real potential to increase the number of patients who can benefit from these ICI treatments by optimising the patient’s gut microbiome.”

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