- IND clearance marks the expansion of 4D pharma’s clinical-stage pipeline of single strain Live Biotherapeutics into neurology

- First US FDA IND clearance for a Live Biotherapeutic for Parkinson’s disease

4D pharma plc (AIM: DDDD, NASDAQ: LBPS), a pharmaceutical company leading the development of Live Biotherapeutic products (LBPs), a novel class of drug derived from the microbiome, today announces that the U.S. Food and Drug Administration (FDA) has cleared investigational new drug (IND) applications for two Live Biotherapeutics (LBPs), MRx0005 and MRx0029, for the treatment of Parkinson’s disease. The Company expects to initiate a first-in-human Phase I clinical trial in people with Parkinson’s disease in mid-2022.

“Entering the clinic with our novel CNS programs stemming from our proprietary MicroRx platform will represent an important step for 4D pharma’s continued growth and leadership in the microbiome field. We believe MRx0005 and MRx0029 are the first ever Live Biotherapeutic products for Parkinson’s to enter the clinic,” said Dr. Alex Stevenson, Chief Scientific Officer, 4D pharma. “Current treatments focus on symptoms but do not address the underlying causes of neurodegeneration. Patients and clinicians are in need of 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.”

“Parkinson’s disease is a devastating condition impacting more than 10 million people globally. As the global population ages, this number will continue to increase. 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 the Phase I clinical trial. “Oral, gut-targeted treatments such as 4D pharma’s Live Biotherapeutics MRx0005 and MRx0029 offer an exciting new way for possibly slowing Parkinson’s disease progression. The development of these potential new therapies is really breaking new ground in the field.”

MRx0005 and MRx0029 are two unique single strain Live Biotheraputic candidates, which 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. In animal models of Parkinsonian syndrome, 4D pharma demonstrated that MRx0005 and MRx0029, respectively protected against the loss of dopamine metabolites and dopamine-producing neurons in the brain.

4D pharma expects to initiate a Phase I clinical trial in mid-2022. The multi-center, randomized, double-blind, placebo-controlled study will evaluate the safety and tolerability of MRx0005 or MRx0029 in separate cohorts of patients with Parkinson’s disease. In addition to safety, the study will measure biomarkers relating to the mechanisms of action of the candidate LBPs.

4D pharma is collaborating with Parkinson's UK, a non-profit organization focused on advancing the understanding of Parkinson's disease and improving treatments, and has established a Patient Advisory Board (PAB) comprised of people living with Parkinson's. Supported by Parkinson's UK, the PAB provides a valuable patient-centric perspective to 4D pharma as it advances its novel Live Biotherapeutics into the clinic to treat neurodegenerative conditions such as Parkinson's. The PAB will also focus on raising awareness of the issues people with Parkinson's face with current treatment options. In addition, 4D pharma is an Industry Partner of the Parkinson's Progression Markers Initiative (PPMI), a landmark study sponsored by The Michael J. Fox Foundation to better understand Parkinson's disease and to identify, develop, and validate biomarkers of Parkinson's disease progression to further the development of disease-modifying therapies.

About MRx0005 and MRx0029

MRx0005 and MRx0029 are oral single strain Live Biotherapeutic products in development for the treatment of neurodegenerative conditions such as Parkinson’s disease via the gut-brain axis. Discovered using 4D pharma’s MicroRx® platform, both have been shown pre-clinically to reduce neuroinflammation including inflammation induced by α-synuclein, and to protect neurons from oxidative stress-induced death. MRx0005 has been shown to upregulate expression of neuroactive molecules and their receptors in vivo, and protected against loss of dopamine metabolites in the brains of mice with induced parkinsonian syndrome. Impaired intestinal barrier function and intestinal permeability is a common symptom of Parkinson’s disease thought to potentially contribute to the onset or progression of the condition, and MRx0029 has been shown to improve intestinal epithelial integrity. MRx0029 has also been shown to induce the differentiation of dopaminergic neuronal phenotype in vitro, and in an animal model of Parkinson’s disease protected against the loss of dopaminergic neurons. In 2022, 4D pharma plans to commence a Phase I clinical trial of both MRx0005 and MRx0029, separately, in people with Parkinson’s disease.

About Parkinson’s disease

Parkinson’s disease is a progressive neurodegenerative condition caused by the loss of dopamine-producing (dopaminergic) neurons in the brain resulting in characteristic motor symptoms of tremor, stiffness, slowed movement and impaired balance and coordination. A number of non-motor symptoms often precede the onset of motor symptoms by years, and gastrointestinal symptoms such as constipation and alterations of the enteric nervous system are experienced by a majority of Parkinson’s patients. Parkinson’s disease is the second most common age-related neurodegenerative disorder after Alzheimer’s disease, affecting an estimated ten million people worldwide. Current treatments focus on replacing dopamine deficiency in the brain or addressing particular non-motor symptoms. However, these treatments are associated with serious side effects and their efficacy can wear off over time. There are currently no approved disease-modifying treatments which prevent, slow or reverse the underlying neurodegenerative processes.

About 4D pharma

4D pharma is a world leader in the development of Live Biotherapeutics, a novel and emerging class of drugs, defined by the FDA as 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 has developed a proprietary platform, MicroRx®, that rationally identifies Live Biotherapeutics based on a deep understanding of function and mechanism.

4D pharma's Live Biotherapeutic products (LBPs) are orally delivered single strains of bacteria that are naturally found in the healthy human gut. The Company has five clinical programs, namely a Phase I/II study of MRx0518 in combination with KEYTRUDA® (pembrolizumab) in solid tumors, a Phase I study of MRx0518 in a neoadjuvant setting for patients with solid tumors, a Phase I study of MRx0518 in patients with pancreatic cancer, a Phase I/II study of MRx-4DP0004 in asthma, and Blautix® in irritable bowel syndrome (IBS) which has completed a successful Phase II trial. A Phase I study of MRx0005 and MRx0029 in patients with Parkinson’s disease is expected to commence in 2022. Additional preclinical-stage programs include candidates for CNS disease, immune-inflammatory conditions and cancer. The Company has a research collaboration with MSD, a tradename of Merck & Co., Inc., Kenilworth, NJ, USA, to discover and develop Live Biotherapeutics for vaccines.

For more information, refer to https://www.4dpharmaplc.com.

Forward-Looking Statements

This announcement contains "forward-looking statements." All statements other than statements of historical fact contained in this announcement, including without limitation statements regarding the efficacy of Live Biotherapeutics including MRx0005 and MRx0029, their ability to impact the treatment of Parkinson’s disease, and the expected timing of the Company’s Phase I clinical trial, are forward-looking statements within the meaning of Section 27A of the United States Securities Act of 1933, as amended (the "Securities Act"), and Section 21E of the United States Securities Exchange Act of 1934, as amended (the "Exchange Act"). Forward-looking statements are often identified by the words "believe," "expect," "anticipate," "plan," "intend," "foresee," "should," "would," "could," "may," "estimate," "outlook" and similar expressions, including the negative thereof. The absence of these words, however, does not mean that the statements are not forward-looking. These forward-looking statements are based on the Company's current expectations, beliefs and assumptions concerning future developments and business conditions and their potential effect on the Company. While management believes that these forward-looking statements are reasonable as and when made, there can be no assurance that future developments affecting the Company will be those that it anticipates.

All of the Company's forward-looking statements involve known and unknown risks and uncertainties, some of which are significant or beyond its control, and assumptions that could cause actual results to differ materially from the Company's historical experience and its present expectations or projections. The foregoing factors and the other risks and uncertainties that affect the Company's business, including the risks relating to the efficacy of its Live Biotherapeutic drug candidates including MRx0005 and MRx0029, risk related to safety of investigational therapeutics, clinical development risk, and those additional risks and uncertainties described the documents filed by the Company with the US Securities and Exchange Commission ("SEC"), should be carefully considered. The Company wishes to caution you not to place undue reliance on any forward-looking statements, which speak only as of the date hereof. The Company undertakes no obligation to publicly update or revise any of its forward-looking statements after the date they are made, whether as a result of new information, future events or otherwise, except to the extent required by law.

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