4D Pharma Presents New Data from Two MRx0518 Clinical Trials at the Society for Immunotherapy of Cancer (SITC) Annual Meeting

MRx0518 demonstrates upregulation of key immune biomarkers associated with anti-cancer activity in neoadjuvant monotherapy setting

Addition of new tumor type cohorts to ongoing Part B of Phase I/II combination trial with pembrolizumab, following 42% disease control rate (DCR) in completed Part A

Company to host virtual KOL event to review data on Wednesday, November 11, 2020 at 1:00pm GMT (8:00am ET)

LEEDS, England–(BUSINESS WIRE)–4D pharma plc (AIM: DDDD), a pharmaceutical company leading the development of Live Biotherapeutic products (LBPs) – a novel class of drug derived from the microbiome, today announces new positive clinical data from two clinical trials of MRx0518, its lead immuno-oncology single strain Live Biotherapeutic candidate. The data is 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 I trial of MRx0518 in the neoadjuvant setting.
• Two further presentations provide updates on the ongoing Phase I/II trial of MRx0518 in combination with Keytruda® (pembrolizumab) in patients refractory to checkpoint inhibitors.
• 4D pharma will also host a virtual key opinion leader (KOL) event to review these data on Wednesday, November 11, 2020 at 1:00pm GMT (8:00am ET).

“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.”

MRx0518 in Neoadjuvant Setting Monotherapy

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The ongoing, two-part Phase I 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 two to four 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<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 and Efficacy data

The ongoing Phase I/II 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, which 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%) 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%. 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% 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 I/II 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.

For more information on the clinical trials see https://clinicaltrials.gov/ct2/show/NCT03934827 and https://clinicaltrials.gov/ct2/show/NCT03637803

Virtual KOL Conference Call and Webcast Event

4D pharma will host a virtual event for investors and analysts to review the data presented from two ongoing clinical trials of MRx0518 at SITC 2020. The event will take place on Wednesday, November 11, 2020 at 1:00pm GMT (8:00am ET) and will feature discussions of data from both trials from Dr. Mark P. Lythgoe, Academic Clinical Fellow in Medical Oncology and Pharmacist at Imperial College London, and Dr. Shubham Pant, Associate Professor Department of Investigational Cancer Therapeutics and Department of Gastrointestinal Medical Oncology at the University of Texas MD Anderson Cancer Center, as well as presentations from 4D management.

A live webcast of the event will be available on the Reports and Presentations section of the 4D pharma website at www.4Dpharmaplc.com. To access the call, please dial 1-877-270-2148 (United States) or 1-412-902-6510 (international) and reference the 4D pharma conference call to join. A replay of the webcast and accompanying slides will be available on the 4D pharma website following the event.

About MRx0518

MRx0518 is single strain Live Biotherapeutic product 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 (pembrolizumab) in patients who have previously progressed on anti PD-1 therapies. The Coordinating Investigator of the study is at The University of Texas MD Anderson Cancer Center, Houston, USA, with multiple additional sites in the US. The study is being conducted in collaboration with MSD, the tradename of Merck & Co., Inc., Kenilworth, NJ, USA. MRx0518-I-003 is in combination with preoperative radiotherapy in resectable pancreatic cancer.

About 4D pharma

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 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 I/II study of MRx0518 in combination with KEYTRUDA (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, a Phase I/II study of MRx-4DP0004 in asthma, a Phase II study of MRx-4DP0004 in patients hospitalised with COVID-19, and Blautix® in Irritable Bowel Syndrome (IBS) which has completed a successful Phase II trial. 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.

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.

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

Contacts

4D pharma
Duncan Peyton, Chief Executive Officer +44 (0)113 895 0130

Investor Relations: [email protected]

Investor Relations
Julie Seidel, Stern Investor Relations, Inc. +1-212-362-1200

[email protected]

N+1 Singer – Nominated Adviser and Joint Broker +44 (0)20 7496 3000

Philip Davies / Justin McKeegan / Iqra Amin (Corporate Finance)

Tom Salvesen (Corporate Broking)

Bryan Garnier & Co. Limited – Joint Broker +44 (0)20 7332 2500

Dominic Wilson / Phil Walker

Image Box Communications
Neil Hunter / Michelle Boxall +44 (0)20 8943 4685

[email protected] / [email protected]