4D Pharma Presents New Data From Two MRx0518 Clinical Trials 

4D pharma plc recently announced new positive clinical data from two clinical trials of MRx0518, its lead immuno-oncology single strain Live Biotherapeutic candidate.  The data was presented in three posters at the Society for Immunotherapy of Cancer (SITC) Annual Meeting 2020, November 9-14, 2020.

-The first poster includes the first data presented for MRx0518 as a monotherapy.  The results are from the completed Part A of a Phase 1 trial of MRx0518 in the neoadjuvant setting.  

-Two further presentations provide updates on the ongoing Phase 1/2 trial of MRx0518 in combination with Keytruda(R) (pembrolizumab) in patients refractory to checkpoint inhibitors. 

“The data generated from both our trials of MRx0518 and presented this week at SITC, in monotherapy and combination with an immune checkpoint inhibitor settings, is further evidence of the potential of 4D’s LBPs in oncology. The strong immunological signals of biological activity shown in the monotherapy trial provides further clinical evidence of the role and contribution of MRx0518 to the impressive results we are seeing in combination with Keytruda in an incredibly difficult to treat patient population,” said Duncan Peyton, Chief Executive Officer of 4D pharma. “The data also furthers and clarifies our earlier work on the mechanism of action of MRx0518 and, importantly, the activity we are seeing in these patients mirrors the preclinical results, further validating our approach and the MicroRx platform.  The data generated from these trials provide us with huge confidence not only with moving forward with MRx0518 as a novel immunotherapy for the treatment of cancer, but also our MicroRx platform. We look forward to advancing our MRx0518 program further into the clinic and we are already enrolling patients into Part B of our Keytruda combination study, including the addition of new tumor type cohorts.”

The ongoing, two-part Phase 1 study is assessing the safety and tolerability of MRx0518 monotherapy in treatment-naïve subjects undergoing surgical resection of solid tumors. The study is designed to generate paired patient samples at diagnostic biopsy and surgical resection, with an intervening period of MRx0518 monotherapy treatment of 2 to 4 weeks.

As of data cut-off at October 10, 2020, 17 patients were evaluable for safety and biomarker analyses. 

Immune Modulation Results

-Following MRx0518 treatment, relative increases in cytotoxic cells, CD8+ T cells and other immune subsets associated with anti-tumor activity were observed in paired tumor samples. 

-Upregulation of key immuno-stimulatory anti-tumor cytokines and chemokines, such as IL-12 and CXCL10, was observed in post-treatment plasma samples. 

Genomic Modulation Results

-Gene expression analysis identified significant expression changes in 98 genes (p less than 0.05) in paired samples as a result of MRx0518 treatment, including upregulation of pathways associated with antigen presentation, costimulatory signaling, cytokine and chemokine signaling, known to promote anti-tumor immune activity. 

Initial Safety Data

-MRx0518 monotherapy was generally well-tolerated with no SAEs or grades 3 or 4 toxicities reported. 

MRx0518 in Combination with Pembrolizumab – Part A Safety & Efficacy data

The ongoing Phase 1/2 open-label, two-part clinical trial is evaluating the safety and preliminary efficacy of MRx0518 in combination with pembrolizumab in heavily pre-treated metastatic patients with solid tumors refractory to immune checkpoint inhibitors. 

The goal of the Part A phase of this study was to assess the safety, tolerability and initial efficacy enrolled a total of 12 heavily pre-treated metastatic renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC) patients refractory to immune checkpoint inhibitors. All patients received a twice daily dose of oral MRx0518 for 3 weeks in combination with a single cycle of pembrolizumab, and assessed for dose-limiting toxicities. Once the treatment cycle was completed, patients were eligible to remain on treatment for up to 2 years to assess clinical benefit.

As of the data cut-off date October 23, 2020, all 12 patients enrolled in Part A of this study were evaluable for safety and preliminary efficacy.

Initial Clinical Activity Data

-MRx0518 in combination with pembrolizumab provided clinical benefit to 5 of 12 (42 percent) patients, defined as a complete response (CR), partial response (PR) or stable disease (SD) for 6 months or longer.

-Of the 5 patients who achieved clinical benefit, 3 patients experienced PR, an overall response rate (ORR) of 25 percent.  Best overall response to prior to immune checkpoint inhibitor treatment for 2 of these patients was stable disease (SD).

-Median progression free survival (PFS) was 2.14 (95 percent CI 0.43, not estimable) months.

Initial Safety Data

-MRx0518 in combination with pembrolizumab was generally well-tolerated with no treatment-related Grades 4 or 5 serious adverse events (SAEs) reported.

-No treatment-related adverse events were attributed to treatment discontinuation. 

MRx0518 in Combination With Pembrolizumab – Part B Ongoing, Addition of New Cohorts

In addition to the new safety and preliminary efficacy data announced today, 4D also presented a trial-in-progress (TIP) poster describing the ongoing Part B cohort expansion phase of the Phase 1/2 clinical trial of MRx0518 in combination with pembrolizumab in patients refractory to immune checkpoint inhibitors.  Today 4D pharma announced additional tumor type cohorts will be enrolled on the study, following the promising clinical benefit results generated in Part A in patients with RCC and NSCLC.

Part B of this study is currently enrolling up to 120 patients with RCC, NSCLC, bladder cancer, triple-negative breast cancer (TNBC), head and neck squamous cell carcinoma (HNSCC) and microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) solid tumors.  Enrollment is expected to complete Q4 2021.

The clinical data from the two MRx0518 clinical trials presented at the SITC Annual Meeting are now available on the Posters and Publications section of the 4D Pharma website at www.4Dpharmaplc.com.

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 (R), 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 six clinical programmes, namely a Phase 1/2 study of MRx0518 in combination with KEYTRUDA (pembrolizumab) in solid tumours, a Phase 1 study of MRx0518 in a neoadjuvant setting for patients with solid tumours, a Phase 1 study of MRx0518 in patients with pancreatic cancer, a Phase 1/2 study of MRx-4DP0004 in asthma, a Phase 2 study of MRx-4DP0004 in patients hospitalized with COVID-19, and Blautix(R) in Irritable Bowel Syndrome (IBS) which has completed a successful Phase 2 trial. Preclinical-stage programs 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, to discover and develop Live Biotherapeutics for vaccines.

In October 2020, 4D Pharma announced its intention to merge with Longevity Acquisition Corporation (NASDAQ: LOAC), a special purpose acquisition company (SPAC), and seek a NASDAQ listing.  The merger is expected to be completed and the NASDAQ listing of 4D Pharma American Depositary Shares (ADSs) under the ticker symbol ‘LBPS’ is currently expected to become effective in early 2021, subject to approval of 4D shareholders and Longevity shareholders, and the SEC review process.