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 programmes 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 programmes in diverse therapeutic areas including immuno-oncology, GI, respiratory, autoimmune and CNS disease.

Solid Tumours - Combination study with Keytruda®

Phase 1

Our immuno-oncology programme is underpinned by a strain which has an immuno-stimulatory host-response profile. We are investigating the effects of this candidate against a wide range of solid tumour types. We are conducting a Phase I study of MRx0518 in combination with Keytruda (pembrolizumab) in solid tumours. For more information about this study please see https://clinicaltrials.gov/ct2/show/NCT03637803 or here

Solid tumours - Monotherapy study (Tx naïve neoadjuvant)

Phase 1

Neoadjuvant treatment in patients undergoing surgical resection of solid tumours. Study expected to commence Q1-Q2 2019

Pancreatic cancer - Monotherapy study (neoadjuvant)

Phase 1

Part of 4D pharma's strategic collaboration with the University of Texas MD Anderson Cancer Center. Expected to open H2 2019

Immuno-oncology

Development

In addiiton to our lead MRx0518 programme, 4D has identified second-generation immuno-oncology LBP candidates with mechanisms appropriate for the treatment of additional tumour types

Immuno-oncology

Development

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

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 successful Phase Ib clinical study of Blautix in IBS patients. We have a Phase II trial in progress. For more information please see https://clinicaltrials.gov/ct2/show/NCT03721107 or here

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

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.

We have a Phase I/II trial in progress. For more information please see https://clinicaltrials.gov/ct2/show/NCT03851250 or here.

Neurodegeneration

Development

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

Vaccines

Discovery

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

Ulcerative Colitis

Development

Ulcerative Colitis (UC) is an inflammatory bowel disease that affects the rectum and colon. Inflammation in UC occurs in the intestinal tract from dysregulated interactions between the microflora of the gut and the mucosa. UC has a unique presentation in children relative to adults. The paediatric form of the disease is widely regarded to be more aggressive than the adult form, and thus leads to increased risks of negative outcomes. Children with UC have higher risks of developing steroid dependency and a higher rate of colectomy than adults. A small percentage of children will go into permanent remission with either medical or surgical management, but most will continue to have persistent disease with acute exacerbations.

Rosburix is a single-strain, human gut commensal bacteria which has an anti-inflammatory mechanism and is under investigation for the treatment of paediatric Ulcerative Colitis.

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 industry standard preclinical models.

Autism

Preclinical

4D is also building on research into the gut-brain-axis to discover and develop live biotherapeutics for the treatment of neurodegenerative disease and autism.

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