Diverse disease areas beyond the gut

It is well understood that the microbiome has a fundamental influence on the immune system, metabolism and potentially the central nervous system. Through our understanding of the functionality and interaction of these bacteria with the human body, Live Biotherapeutics developed by 4D pharma have the potential to treat a large number of diseases.

Different organisms; distinct mechanisms

Each of our programs is underpinned by a different Live Biotherapeutic, and each operates through a variety of different mechanisms. Using MicroRx® , we are able to gain an understanding of how our candidates impact the human body at the molecular level. This allows us to more effectively target diseases for intervention with our Live Biotherapeutics. Additionally, using MicroDx, we can assess how those candidates impact the host microbiome.

Current pipeline

Using MicroRx®, we have generated a suite of development programs in diverse therapeutic areas including immuno-oncology, GI, respiratory, autoimmune and CNS disease.

Solid Tumors - Combination with Keytruda®

Phase 2

We are conducting a Phase I/II study of MRx0518 in combination with Keytruda (pembrolizumab) in patients with heavily pre-treated solid tumors secondary resistant to immune checkpoint inhibitors like Keytruda®.

In Part A of the study, the combination achieved a disease control rate of 42%, and demonstrated good safety and tolerability. Part B cohort expansion phase is ongoing in RCC, NSCLC, bladder cancer, TNBC, HNSCC and MSI-H/dMMR solid tumors.

For more information about this study please see https://clinicaltrials.gov/ct2/show/NCT03637803 or here

Urothelial carcinoma - Combination with Bavencio®

Phase 2

Under a clinical trial collaboration and supply agreement with Merck KGaA, Darmstadt, Germany and Pfizer Inc., 4D pharma intends to commence a clinical trial to evaluate anti-PD-L1 immune checkpoint inhibitor Bavencio® (avelumab) in combination with MRx0518 as a first-line maintenance therapy for patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy.

Solid tumours - Monotherapy study (Tx naïve neoadjuvant)

Phase 1

We are conducting a trial of MRx0518 as a neoadjuvant monotherapy in previously untreated patients undergoing surgical resection of solid tumors, in collaboration with Imperial College London.

Results from Part A of the study demonstrated increases in key immune biomarkers associated with anti-cancer immune response, response to therapy, and better clinical outcomes.

Pancreatic cancer - Combination with radiotherapy

Phase 1

This study will assess the combination of MRx0518 with preoperative radiotherapy in patients with resectable pancreatic cancer.
The trial is part of 4D pharma's strategic collaboration with the University of Texas MD Anderson Cancer Center.

Immuno-oncology

Development

In addition to our lead MRx0518 program, 4D has identified second-generation immuno-oncology LBP candidates with mechanisms potentially appropriate for the treatment of additional tumor types

Neurodegeneration

Development

4D is building on research into the gut-brain-axis to discover and develop live biotherapeutics for the treatment of neurodegenerative diseases such as Parkinson's.

Neurodegeneration

Development

4D is building on research into the gut-brain-axis to discover and develop live biotherapeutics for the treatment of neurodegenerative diseases such as Parkinson's.

Neurodevelopmental/Psychiatric disorders

Preclinical

4D is building on research into the gut-brain-axis to discover and develop live biotherapeutics for the treatment of neurodevelopmental and psychiatric disorders.

4D has demonstrated the ability of an orally administered, gut-restricted Live Biotherapeutic to achieve statistically significant effects in a range of tests that assessed autism-like behaviors in animal models. The strain has also been shown to upregulate the expression of neuropeptides implicated in social behaviors.

Asthma

Phase 1

Severe asthmatics constitute 5-10% of the overall asthma population and have significant unmet need. These patients are unable to control their symptoms using the maximum dose of inhalers and bronchodilators and require add-on therapy to ameliorate exacerbations. In particular, patients who present with a neutrophilic phenotype have very limited treatment options. Our lead candidate shows profound efficacy in preclinical models of severe asthma.

A Phase I/II trial of MRx-4DP0004 in asthma is in progress.

For more information please see https://clinicaltrials.gov/ct2/show/NCT03851250 or here.

Rheumatoid arthritis

Development

Rheumatoid arthritis (RA) is an autoimmune disease of the joints which affects more than 3 million people in the US and major EU markets. Despite the launch of numerous RA therapeutics, there are still a significant number of patients who require safe and effective treatment options.

Our lead Live Biotherapeutic candidate for RA shows both anti-inflammatory and joint-protective effects in preclinical models.

Multiple sclerosis

Development

Multiple sclerosis (MS) is a disease resulting from the attack of the insulating coating of nerve cells – known as the myelin sheath – by the immune system. There is currently no cure for MS and most patients need to take medications chronically throughout their lives. Although there are a number of treatments available for MS patients, they are associated with significant side-effects.

The company’s Live Biotherapeutic candidate in MS has shown strong efficacy in multiple industry standard preclinical models.

Irritable bowel syndrome

Phase 2

Irritable bowel syndrome (IBS) is a common bowel disorder which affects around 10-15% of the population. The condition is characterised by abdominal pain, bloating and changes in bowel frequency. The causes of IBS are multi-faceted; however, it is becoming increasingly clear that the gut microbiota plays a key role in driving the disease. Existing treatments for IBS focus on symptom management, and there are currently no available therapeutics which tackle the underlying causes of IBS.

Blautix is a single-strain human gut commensal bacteria with a distinctive metabolism which may allow the treatment of IBS. Inside the gut, Blautix consumes gases which are known to cause bloating, abdominal pain and changes in bowel frequency.

We have completed a Phase II trial, in which Blautix demonstrated signals of clinical activity in both IBS-C and IBS-D, and a highly favorable safety and tolerability profile.

Crohn’s disease

Phase 1

Crohn’s disease is an inflammatory bowel disease which can occur in any part of the gastro-intestinal tract, but primarily affects the small intestine. Approximately 20-30% of all Crohn’s disease patients present when they are younger than 20 years old and the manifestation of the disease in the paediatric population is clinically distinct. Patients suffer from diarrhoea, rectal bleeding and abdominal pain with many also experiencing weight loss, malnutrition and pubertal delay. Many of the standard therapies used in the adult population are problematic in children, including steroids and other systemic immunosuppressants which can exacerbate growth retardation.

Thetanix is a single-strain human gut commensal bacteria which has an anti-inflammatory mechanism and is under investigation for the treatment of paediatric Crohn’s disease. Thetanix specifically targets the lower bowel – the region of most severe disease in children.

We have successfully completed a Phase Ib clinical study in paediatric patients

Vaccines, collaboration with MSD

Preclinical

We have entered a research collaboration and option agreement with MSD, utilizing the MicroRx platform to discover and develop LBPs as novel vaccines

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