On November 6, 2019 4D Pharma plc (AIM: DDDD), a leading-edge pharmaceutical company in the development of live biotherapeutics, reported preliminary safety and clinical observations from an ongoing clinical phase -I / II study, in collaboration with MSD, a trade name of Merck & Co., Inc. of Kenilworth, NJUSA, in conjunction with its leading oncology candidate, Mrx0518, in combination with the MSD anti-PD-1 therapy with KEYTRUDA (pembrolizumab) in patients with advanced malignancies who previously responded and whose disease was subsequently co-administered PD-1 / PD-L1 inhibitors has progressed to evaluate (Press release, 4d Pharma, NOV 6, 2019, View Source;814041836.html [SID1234550511]). These are the first observations of an oncology study in humans with a live biotherapy product.

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Important observations:

Initial data from the first six patients show that the combination of Mrx0518 and KEYTRUDA is well tolerated.
Induction of clinically relevant response in two out of six patients with previous progressive disease
Three patients had to retire for illness-related reasons (two after the diagnosis of a progressive illness and one due to a disease-related adverse event).
The Phase I / II trial is an open-label study evaluating the safety and preliminary efficacy of Mrx0518 and KEYTRUDA in patients with renal cell carcinoma (RCC), melanoma, non-small cell lung cancer (NSCLC) and bladder cancer who have resistance against PD-1 / PD-L1 inhibitors. In preclinical studies, Mrx0518 has previously demonstrated significant efficacy as a monotherapy and as a combination therapy with the checkpoint therapy. Mrx0518 has also been shown to be an effective immune stimulant and capable of increasing the number of tumor infiltrating lymphocytes (TILs) that have been shown to be anticancer in preclinical cancer models.

Although the checkpoint therapies have proven to be effective anti-cancer treatments, they are not effective in all patients, and those who respond may develop resistance over time, leading to a loss of efficacy and progression of the disease Disease leads. The mode of action of Mrx0518 has the potential to reactivate the efficacy of checkpoint therapies, and this study was designed to investigate this effect in patients with advanced metastatic disease.

Patients eligible for the Phase I / II trial must have a progressive disease prior to enrollment, which has been confirmed by two residual scans. Part A of the study aims to enroll 12 patients, with the primary outcome being measurement of safety and tolerability. Part A will be performed over three weeks and patients will receive one cycle of KEYTRUDA, taking Mrx0518 orally twice a day (the "offer") .After completion of the first cycle, patients will be eligible for up to 35 cycles of KEYTRUDA in the drug combination (over about two years) or until disease progression occurs Patients routinely have restaging scans every nine weeks More information on the study can be found at the end of this announcement.

The clinical observations of the first six patients in Part A include:

Two patients showed partial response (according to RECIST version 1.11 criteria) with evidence of tumor disappearance and continue to participate in the study (one patient has been in the study for more than six months).
In another patient, the disease is stable and continues to participate in the study.
Two patients were excluded from the study because of a progressive disease.
One patient was excluded prior to the restaging scan for a serious disease-related adverse event.
The only patient currently tested for tumor biomarker showed signs of increased TIL after treatment (approval for biomarker assessment is optional).
No serious adverse drug reactions were noted.
Dr. Alex Stevenson, Chief Scientific Officer of 4D, said, "We are very encouraged by these early signs of activity in the combination of Mrx0518 and KEYTRUDA in patients with advanced disease. One third of patients who had previously stopped responding to PD-1 inhibitors and had a progressive disease have now shown clinical benefit. There is also a first indication in a patient suggesting that the treatment is capable of increasing the number of tumor infiltrating lymphocytes in a clinical setting, which is in line with our preclinical results. Although more work will be required to determine the robustness of the observed responses and their frequency in a larger number of patients, we are pleased to to report these initial results – the first from an oncological study with a live biotherapeutic. The open label trial continues and we will continue to review the data to optimize our future development strategy for Mrx0518 in these indications.

"These first results further support our ongoing investment in our oncology franchise. We plan to include Mrx0518 in additional clinical trials of various tumor types and settings, either in combination or as monotherapy. The next study with Mrx0518 in combination with radiotherapy for pancreatic cancer will start at MD Anderson before the end of this year. In addition, we continue to develop live biotherapeutic candidates with different modes of action for oncology applications. The first, MRx1299, is currently in GMP manufacturing development. "

Notes:
1 Criteria for assessing response to solid tumors

This notice contains inside information as defined in Article 7 of the Market Abuse Regulation (MAR) No 596/2014. The person responsible for making this announcement on behalf of the Company is Duncan Peyton . After the publication of this notice, this inside information will be considered publicly available.