4D pharma plc announced additional clinical data from Part A of its Phase I/II trial of MRx-4DP0004, an orally-delivered single strain Live Biotherapeutic being developed for the treatment of asthma. The Company previously reported topline safety and efficacy data from Part A, and announced additional details of these results. The Phase I/II trial is a multi-center, double-blind, placebo-controlled study in patients with partly controlled asthma taking long-term medication.

The primary endpoint of Part A was to evaluate the safety and tolerability of MRx-4DP0004. Secondary endpoints evaluating clinical activity include Asthma Control Questionnaire (ACQ-6), use of short-acting beta agonist (SABA) rescue medication, Asthma Quality of Life Questionnaire (AQLQ), lung function, and exacerbations. As previously announced, Part A met the primary endpoint and the safety profile of MRx-4DP0004 was comparable to placebo.

In addition, MRx-4DP0004 showed activity across multiple secondary endpoints compared to placebo, generating promising preliminary signals of clinical activity which support progression into Part B of the Phase I/II study. Part B is expected to enroll up to 90 patients and will assess clinical efficacy in addition to exploratory immune and microbiome biomarkers. MRx-4DP0004 Phase I/II Trial Overview and Results from Part A - Part A of the Phase I/II clinical trial enrolled 34 patients, randomized 1:1 to receive oral MRx-4DP0004 (N=18) or placebo (N=16) twice daily for 12 weeks, in addition to their usual maintenance therapy of inhaled corticosteroids (ICS) with or without long-acting beta agonist (LABA).

MRx-4DP0004 achieved the primary endpoint of safety and tolerability in combination with ICS and LABA. 61.1% of patients receiving MRx-4DP0004 experienced any adverse event (AE) compared to 75.0% of patients receiving placebo, of which only two were possibly related to MRx-4DP0004. All AEs were mild or moderate in severity.

No serious adverse events (SAEs) related to treatment were reported. At all timepoints throughout the treatment period, a significantly greater proportion of MRx-4DP0004 treated patients experienced reductions from baseline in Asthma Control Questionnaire (ACQ-6) score, as compared to placebo. At end of treatment, 83.3% of patients receiving MRx-4DP0004 experienced reductions in ACQ-6 score, compared to 56.3% in the placebo arm.

The proportion of patients with reductions in ACQ-6 score at end of treatment will be the primary endpoint for Part B of the Phase I/II trial. Moreover, at end of treatment, 50.0% of patients receiving MRx-4DP0004 experienced reductions from baseline in ACQ-6 scores of 0.5 or more, compared to 37.5% in the placebo arm. At the end of treatment, 50% of patients receiving MRx-4DP0004 reduced their use of SABA, compared to 18.8% of patients receiving placebo.

Overreliance on SABA rescue medication is associated with a greater risk of exacerbations, hospitalizations and mortality, and reduced SABA use is a key indicator of improved asthma control. 50.0% of patients receiving MRx-4DP0004 experienced a clinically meaningful increase in Asthma Quality of Life Questionnaire (AQLQ) scores of =0.5 at end of treatment, compared to 31.3% receiving placebo. MRx-4DP0004-treated patients' quality of life continued to improve over the treatment period.

Mean measures of lung function including forced expiratory volume in the first second (FEV1, percentage of predicted), peak expiratory flow (PEF), and ratio of FEV1 to forced vital capacity (FEV1/FVC) for both MRx-4DP0004 and placebo treatment arms generally remained within normal ranges from baseline to end of treatment. One of 18 patients (5.6%) randomized to MRx-4DP0004 experienced an asthma exacerbation, compared to two of 16 patients (12.5%) randomized to placebo. MRx-4DP0004 is an oral, immunomodulatory, single strain Live Biotherapeutic product.

4D pharma has demonstrated the ability of MRx-4DP0004 ability to reduce airway inflammation in a pre-clinical model of severe asthma. This is achieved through a concurrent reduction in both neutrophilic and eosinophilic infiltration and inflammation. MRx-4DP0004 is currently being evaluated in a two-part, randomized, double-blinded, placebo-controlled study evaluating the safety, tolerability and efficacy of MRx-4DP0004 in patients with partly controlled asthma (Clinical Trial identifier: NCT03851250).