4D Pharma to trial LBPs in patients with Parkinson’s disease: ‘We are continuing to expand clinical pathways for the microbiome field’

22-Feb-2022 - Last updated on 22-Feb-2022 at 13:35 GMT

4D Pharma says the US Food and Drug Administration (FDA) has cleared its IND application for the first in-human trial to use Live Biotherapeutics (LBPs) for the treatment of Parkinson’s disease.

The UK headquartered company, which has been NASDAQ listed since March 2021, expects to initiate a Phase I clinical trial, evaluating its bacterial strains, MRx0005 and MRx0029, in individuals with Parkinson’s disease in mid-2022.

Speaking to this publication in December 2021, Duncan Peyton, CEO, 4D Pharma, said the company worked with Parkinson’s UK and the Michael J Fox Foundation to help design the trial.

The study will have a small cohort of participants - around 40 patients - and will be run simultaneously at sites in the UK and the US, said Dr Alex Stevenson, chief scientific officer, 4D Pharma.

"As a first-in-human study the primary endpoint will naturally be safety and tolerability, though notably in patient rather than healthy volunteers. The study will also include a number of exploratory GI, immune and metabolomics endpoints to generate translational data relating to the mechanism of action of the two drug candidates and inform subsequent clinical development," he told BioPharma-Reporter.

Current treatments focus on symptoms but do not address the underlying causes of neurodegeneration, he said.

"Patients and clinicians need new, more effective treatment options, and the gut-brain axis is an exciting area of innovation with the potential to change the way we approach Parkinson’s treatment. We believe that our LBPs MRx0005 and MRx0029, which each have different mechanisms of action worthy of investigation, provide a unique opportunity to address the high unmet needs of those living with Parkinson’s disease.”

Live biotherapeutics, a novel class of drug derived from the microbiome, are defined by the FDA as being biological products that contain a live organism, such as a bacterium, that is applicable to the prevention, treatment or cure of a disease.

4D Pharma says it is using the expertise acquired from its clinical successes in oncology, asthma, and GI to provide new therapeutic solutions in neurology and Parkinson’s, in particular.

Gut-brain axis

There is growing evidence suggesting that the gut-brain axis could be key to developing new treatments for several neurological disorders, particularly Parkinson’s disease, said Professor Peter LeWitt, Sastry Foundation Endowed Chair in Neurology at Wayne State University School of Medicine, and coordinating investigator of 4D Pharma’s Phase I clinical trial.

Oral, gut-targeted treatments such as 4D pharma’s strains offer the possibility of slowing Parkinson’s disease progression, he added.

MRx0005 and MRx0029 have been shown, pre-clinically, to have positive impacts on multiple key aspects of Parkinson’s disease pathology, including gut barrier integrity, neuroinflammation, oxidative stress and neuroprotection, said the company. In animal models of Parkinsonian syndrome, MRx0005 and MRx0029, respectively, protected against the loss of dopamine metabolites and dopamine-producing neurons in the brain, reported the developer.

Asthma trial

4D Pharma continues to progress its clinical development work in relation to other indications.

Last month saw the company announce the release of additional data from Part A of its Phase I/II trial of MRx-4DP0004, its LPB strain being developed for the treatment of asthma, following on from the data it published in December 2021, showing that Part A met the primary endpoint and the safety profile of MRx-4DP0004 was comparable to placebo.

The January 2022 data illustrated that MRx-4DP0004 showed activity across multiple secondary endpoints compared to placebo, generating promising preliminary signals of clinical activity which support progression into Part B of the Phase I/II study, said the company.

Part B is expected to enroll up to 90 patients and will assess clinical efficacy in addition to exploratory immune and microbiome biomarkers.

Following the release of the asthma trial findings at the end of last year, Peyton told us: “Asthma is a huge disease and it affects a lot of people globally. It is a big target area and there hasn’t been a lot of developers getting into this space over the past decade or so. We are enthused about MRx-4DP0004 because of the safety profile, but what we also saw is that it just allowed patients to have a slightly better lifestyle. They could breathe easier, they were less reliant on their rescue meds, which, for an asthma patient, is a big deal.”