DDDD.L Regulatory News (DDDD)

4D pharma plc

(the "Company" or "4D")

Preliminary safety and clinical observations from its Phase I/II study of MRx0518 in combination with KEYTRUDA®  

4D pharma plc (AIM: DDDD), a clinical-stage pharmaceutical company leading the development of Live Biotherapeutics, today announced preliminary safety and clinical observations from an ongoing Phase I/II clinical trial, in collaboration with MSD, a tradename of Merck & Co., Inc., Kenilworth, NJ, USA, to evaluate its lead oncology candidate, MRx0518, in combination with MSD's anti-PD-1 therapy KEYTRUDA® (pembrolizumab), in patients with advanced malignancies who have previously responded and whose disease has then progressed on PD-1/PD-L1 inhibitors. These are the first observations from an oncology study in man involving a Live Biotherapeutic Product.

Key observations:

·; Initial data from the first six patients shows MRx0518 and KEYTRUDA® combination is well tolerated

·; Induction of clinically relevant response in two out of six patients with prior progressive disease

·; Three patients withdrawn for disease related reasons (two following diagnosis of progressive disease and one due to a disease related adverse event)

The Phase I/II study is an open label study to evaluate 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 developed resistance to PD-1/PD-L1 inhibitors. In preclinical studies, MRx0518 has previously shown significant efficacy as a monotherapy and as a combination treatment with checkpoint therapy. MRx0518 has also been shown to be a potent immunostimulant and capable of increasing the number of tumour infiltrating lymphocytes (TILs) associated with an anti-cancer effect in preclinical cancer models. Higher numbers of such TILs are generally considered to be a positive prognostic indicator for the clinical outcome of checkpoint therapies, such as KEYTRUDA®.

Whilst checkpoint therapies have emerged as potent anti-cancer treatments, they are not effective in all patients and those who do respond can develop resistance over time, leading to a loss of efficacy and disease progression. The mode of action of MRx0518 has the potential to reactivate the efficacy of checkpoint therapies and this study has been designed to investigate this effect in patients with advanced metastatic disease.

Eligible patients in the Phase I/II study must have progressive disease, confirmed by two restaging scans, prior to entry into the study. Part A of the study is intended to enrol 12 patients with the primary outcome being to measure safety and tolerability. Part A is carried out over three weeks and patients receive one cycle of KEYTRUDA®, with MRx0518 being taken orally twice a day ('bid'). Following completion of the first cycle, patients are eligible to remain on the drug combination for up to thirty-five cycles of KEYTRUDA® (approximately two years), or until disease progression occurs. Patients routinely have restaging scans every nine weeks. Further information on the study is included at the foot of this announcement.

Clinical observations from the first six patients in part A include:

·; Two patients have shown a partial response (according to the RECIST v1.1 criteria1) with evidence of tumour shrinkage and remain on study (with one patient being on study for over six months)

·; One additional patient has disease that is stable and remains on study

·; Two patients were withdrawn from the study due to progressive disease

·; One patient was withdrawn due to a disease-related serious adverse event prior to the restaging scan

·; The only patient currently assessed for tumour biomarkers showed evidence of increased TIL following treatment (consent for biomarker assessment is optional)

·; No drug related serious adverse events have been noted.

Chief Scientific Officer of 4D, Dr. Alex Stevenson, said "We are very encouraged by these early signals of activity for the MRx0518 and KEYTRUDA® combination in patients with advanced disease. One third of patients who had previously stopped responding to PD-1 inhibitors and had progressive disease have now demonstrated a clinical benefit. There is also an initial signal in one patient suggesting that treatment is able to increase the number of tumour infiltrating lymphocytes in a clinical setting, which is consistent with our preclinical findings. Although more work will be required to establish the robustness of the responses observed and their frequency in a larger number of patients, we are pleased to be able to report these initial results - the first from an oncology study involving a Live Biotherapeutic Product. The open label study is ongoing and we will be reviewing data on a continual basis to optimise our future development strategy for MRx0518 in these indications.

These initial findings further support our continued investment into our oncology franchise. We plan to take MRx0518 into additional clinical studies involving different tumour types and settings, either in combination or as a monotherapy. The next study with MRx0518, in combination with radiotherapy in pancreatic cancer, is planned to commence at MD Anderson before the end of the year. In addition, we continue to develop new Live Biotherapeutic candidates, with distinct modes of action, for oncology applications. The first of these, MRx1299, is currently in GMP manufacturing development."

Notes:

1 Response Evaluation Criteria in Solid Tumours