4D pharma presents additional interim clinical data from combination study for lead oncology candidate

First global clinical confirmation of a live biotherapeutic product (LBP) initiating a response in cancer patients

Leeds, UK, March 17, 2020 - 4D pharma plc (AIM: DDDD), a pharmaceutical company leading the development of Live Biotherapeutics, today announces an update on the previously reported interim data from an ongoing phase I/II clinical trial, in collaboration with MSD, a tradename of Merck & Co., Inc., Kenilworth, NJ, USA, to evaluate 4D pharma’s lead oncology candidate, MRx0518, in combination with MSD's anti-PD-1 therapy KEYTRUDA(R) (pembrolizumab), in patients with advanced malignancies who have previously responded and whose disease has then progressed on PD-1/PD-L1 inhibitors. 

The additional data has been presented to delegates of Chardan’s virtual 2nd Annual Microbiome Medicines Summit, on March 16, 2020. The data was presented by Duncan Peyton, CEO and Alex Stevenson, CSO, 4D pharma. The presentation provides additional detail on headline interim results from the phase I/II clinical trial announced on November 6, 2019.  The trial is being conducted, and data compiled at MD Anderson, University of Texas, US. 

The data is the first global clinical confirmation of a live biotherapeutic product (LBP) initiating a response in cancer patients. The patients in the live biotherapeutic clinical trial had all previously received multiple lines of treatment with little efficacy, exhausting all currently approved treatment options. 4D pharma believes that the data provide evidence that adding the Company’s product, MRx0518, to the checkpoint inhibitor treatment regimen can induce tumor responses in patients who have previously become refractory to these therapies. 4D believes that, if demonstrated in larger studies, the addition of MRx0518 to checkpoint therapy will enable approved checkpoint inhibitors to work more effectively, for a longer duration, and in a wider patient population. 

The phase I/II 4D pharma study is an open label trial to evaluate the safety and preliminary efficacy of MRx0518 and KEYTRUDA(R) in patients with renal cell carcinoma (RCC), melanoma, non-small cell lung cancer (NSCLC) and bladder cancer, who have developed resistance to PD-1/PD-L1 inhibitors. Checkpoint therapies, whilst capable of producing durable anti-tumor responses, are not effective in all patients. In addition, those who do respond can develop resistance over time, leading to disease progression. The study has been designed to investigate this effect in patients with advanced metastatic disease.

Clinical observations from the first six patients in part A were presented, including:

• Two partial responses (PR) with evidence of tumor shrinkage who remain on study (one patient for over 10 months) 
• One patient with stable disease (SD), remains on study for over eight months 
• Evidence of increased tumor-infiltrating lymphocytes (TILs) following treatment 
• No drug related serious adverse events 

Specifically, one stage IV NSCLC patient had received seven lines of therapy over nearly three years with little response. In this patient the combination of MRx0518 + KEYTRUDA(R) achieved an overall 51% reduction in target tumors at last assessment. The patient has now been on drug for 41 weeks. 

“The further interim data from the Phase I/II trial provide significant potential for fresh treatment options for oncology patients that have exhausted all other currently approved therapies,” said Duncan Peyton, CEO, 4D pharma. 4D pharma is now delivering the first global clinical evidence of the therapeutic potential of oral live biotherapeutics in cancer. This confirms the significant impact of microbiome immuno-oncology to the pharmaceutical industry in providing additional treatments for patients with underserved needs and little available therapeutic options. This clinical validation of live biotherapeutics to impact diseases external to the gut significantly supports our wider clinical pipeline in other areas such as neurodegeneration and other cancers.” 

Recruitment for the trial continues to progress as expected, with recruitment for Part A now completed. 4D expects to announce data for all 12 Part A subjects in Q2 and to commence enrolment for Part B, which will expand the study based on the Part A data. It is expected that the study will be expanded to additional international trial locations and sites, initially in the US. 4D pharma also expects to discuss the findings from Part A and avenues for accelerated development with the regulatory agencies.  

 About 4D

Founded in February 2014, 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 has developed a proprietary platform, MicroRx®, that rationally identifies Live Biotherapeutics based on a deep understanding of function and mechanism.

4D's Live Biotherapeutic Products are orally delivered single strains of bacteria that are naturally found in the healthy human gut. The Company has five clinical studies in progress, namely a Phase II clinical study of BLAUTIX(R) in Irritable Bowel Syndrome (IBS), a Phase I/II study of MRx0518 in combination with KEYTRUDA(R) (pembrolizumab) in solid tumours, a Phase I study of MRx0518 in a neoadjuvant setting for patients with solid tumours, a Phase I study of MRx0518 in patients with pancreatic cancer and a Phase I/II study of MRx-4DP0004 in asthma. Preclinical-stage programmes include candidates for CNS disease such as Parkinson's disease and other neurodegenerative conditions. 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.

About MRx0518

MRx0518, a product of 4D's discovery platform MicroRx(R), is a single strain Live Biotherapeutic Product (LBP) in development for the treatment of cancer. It is delivered as an oral capsule and stimulates the body's immune system, directing it to produce cytokines and immune cells that are known to attack tumours.

It is currently being evaluated in three clinical trials in cancer patients. MRx0518-I-001 is a neoadjuvant monotherapy study in a variety of solid tumours and is being conducted at Imperial College (London, UK). MRx0518-I-002 is in combination with KEYTRUDA(R) (pembrolizumab) in collaboration with MSD, a tradename of Merck & Co., Inc., Kenilworth, NJ, USA. MRx0518-I-003 is a study in combination with radiotherapy in patients with resectable pancreatic cancer.