Immupharma Regulatory News (IMM)

17 April 2018

This announcement contains inside information for the purposes of Article 7 of Regulation (EU) 596/2014.

ImmuPharma PLC

("ImmuPharma" or the "Company")

Topline results of Lupuzor™ Pivotal Phase III Trial

ImmuPharma PLC (LSE:IMM), the specialist drug discovery and development company, announces the results of its pivotal Phase III trial of Lupuzor™, its lead programme for the potential breakthrough compound for Lupus.

Key highlights:

· Lupuzor™ demonstrated a superior response rate over placebo* (52.5% vs 44.6% "responders"**) in the primary analysis on the Full Analysis Set of all 202 patients (including withdrawals who are considered non-responders). However, due to a high response rate in the placebo group, this superior response did not allow statistical significance to be reached (p = 0.2631) and the trial's primary end point was not met.

· Lupuzor™ also demonstrated a superior response rate over placebo (68.8% vs 59.2%) in the 153 patients who completed the study (p value not currently available). 

· Importantly, in patients who had anti-dsDNA autoantibodies (a recognised biomarker for Systemic Lupus Erythematosus ('SLE')), Lupuzor™ demonstrated a superior response rate over placebo (61.5% vs 47.3%, p = 0.0967). In addition, 7.6% of these patients in the Lupuzor™ group went into full remission versus none in the placebo group.

· The study confirmed the outstanding safety profile of Lupuzor™, with zero serious adverse events reported.

· The Company believes these topline results provide evidence for the continued investigation into the development and commercialisation of Lupuzor™ as it has the potential to offer patients and physicians a much needed effective and safe treatment for Lupus.

* Based on the protocol and the commonly accepted study design, there were two groups of patients: (1) patients receiving Lupuzor™ plus "Standard of Care" and (2) patients receiving placebo plus "Standard of Care". "Standard of Care" includes treatment with other drugs such as steroids, anti-malarials, methotrexate etc. It is important to note that when reference is made to placebo, there are no patients who were treated just with placebo, but all were receiving other drug treatments.

** The definition of a "responder" is based on the SLE Responder Index (SRI-4) score, which requires a reduction of at least four points in this score. Therefore, patients who improve by less than four points are counted as non-responders, but also no distinction is made between patients who improve by more than 4 points, all being equal "responders".

Separately, as previously announced, following requests from both Investigators and patients involved in the Phase III study, ImmuPharma has initiated an additional study permitting all patients who participated in the Phase III study, to receive Lupuzor™ (plus "Standard of Care") for six months in an open-label scheme. The results will be gathered as an "extension" open label study, independent of the pivotal Phase III trial. The Company looks forward to providing further updates regarding this study in due course.

Next Steps

The Board believes that there is a significant opportunity for an efficacious and safe treatment for lupus patients given the treatment alternatives currently available, and that there is a desire from both physicians and patients for such a treatment, as evidenced by the investigator and patient-led extension study described above. The Company will undertake a review of the pivotal study's full dataset and will work with its regulatory advisers to determine the optimal next steps.

Following expressions of interest in the Lupuzor™ programme and the Phase III study, ImmuPharma is in ongoing discussions with a number of larger pharmaceutical companies. The results of this study will now be shared with those potential commercial partners. There can be no certainty as to the outcome or timing of these discussions.

The Company will provide further updates on its clinical/regulatory and commercial strategy for Lupuzor™ as appropriate going forward.

Commenting on the results, Dr Robert Zimmer MD, PhD, Chief Scientific Officer said: "The study demonstrated that Lupuzor™ had a superior response rate over placebo and has an outstanding safety profile. The results in the anti-dsDNA antibody positive group are also encouraging. As we receive further data, we will analyse them and work with our regulatory advisers to agree the optimum way forward."

Professor Sylviane Muller PhD, Research Director at the CNRS commented "The results of the study show the potential benefits that can be delivered to patients taking Lupuzor™. In addition, we believe these results have added further evidence to pre-clinical data we have generated to support the development of Lupuzor™ in a number of other auto-immune diseases."

Tim McCarthy, Chairman added: "Lupuzor™ has demonstrated, in this study, a superior response rate over placebo and its exceptional safety, giving it, we believe, a compelling product profile. Whilst we are disappointed at the high response in the placebo plus Standard of Care group that resulted in statistical significance not being reached between the two treatment groups, we believe Lupuzor™ has the potential to bring a much needed safe treatment to the millions of Lupus sufferers around the world. We look forward to providing our shareholders with further updates in due course."

Dimitri Dimitriou, Chief Executive Officer added: "It is an achievement for a small biotech company to complete a phase III trial. We will now be actively following up with all the pharmaceutical companies that have expressed interest in Lupuzor™ and its commercial potential."

For more information on the trial please visit: https://clinicaltrials.gov/ct2/show/NCT02504645

-Ends-

Notes to Editors

ImmuPharma PLC 

ImmuPharma is a pharmaceutical development company listed since 2006 on AIM of the London Stock Exchange (AIM: IMM), focusing on developing novel medicines with high sales potential in specialist markets with serious unmet need. ImmuPharma is led by a commercially focused Board and management team with extensive experience.

Lupuzor™

Lupuzor™ (also referred to as Forigerimod, or P140) is ImmuPharma's lead compound and a potential treatment for lupus (or Systemic Lupus Erythematosus), a chronic, potentially life-threatening auto-immune disease. Lupuzor™ has a novel mechanism of action aimed at modulating the body's immune system so that it does not attack healthy cells, and avoids causing adverse side effects. It has the potential to halt the progression of the disease in a substantial proportion of patients.

Lupuzor™ has been granted Fast Track status by the US FDA and approval to start Phase III under Special Protocol Assessment (SPA) comprising of two phase III trials. This SPA was subsequently amended due to its strong safety and efficacy profile to allow for a reduced number of patients in the pivotal Phase III trial thereby reducing the projected cost and time of development considerably.

The recently completed pivotal Phase III clinical trial was entitled "A 52-Week, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of a 200-mcg Dose of IPP-201101 Plus Standard of Care in Patients With Systemic Lupus Erythematosus".

Commercial Opportunity

There are an estimated five million people globally suffering from Lupus, with approximately 1.5 million patients in the US, Europe and Japan (Source: Lupus Foundation of America). Current 'standard of care' treatments, including steroids and immunosuppressants, can potentially have either serious side effects for patients or limited effectiveness, with over 60% of patients not adequately treated. If Lupuzor™ is approved, it will be entering a market with the potential for multi-billion dollar sales.

P140/Forigerimod in other indications

ImmuPharma together with Professor Sylviane Muller, Lupuzor's inventor, have presented new evidence supporting Lupuzor's™ Forigerimod / P140 peptide activity in several other major auto-immune disease indications outside of Lupus. In particular, the peptide appears to have general effects against auto-immune and even chronic inflammatory indications and pre-clinical evidence supports the molecule's use in: Neuropsychiatric lupus (NPSLE); Gougerot-Sjögren Syndrome (GSS); Guillain-Barré Syndrome; Chronic Inflammatory Demyelinating Polyneuropathy; Arthritis; Crohn's Disease and Asthma.

Oncology and Ophthalmology

ImmuPharma's second most advanced pipeline programme, IPP-204106, is a potential treatment for various cancers and acts by modulating angiogenesis and proliferation. The programme involves the development of synthetic peptides, Nucants, which target certain nuclear proteins such as nucleolin and nucleophosmin on the surface of cells, with very high affinity and selectivity. Nucleolin is a protein which controls critical pathways within the cell. The protein is over-expressed at the surface of dividing cells which makes its binding with Nucants very attractive because of its potential selectivity - this is of particular importance in tumour targeting. It has been recently demonstrated (published in Cancer Res) that the Nucants improve the vascularisation of tumours, increasing thereby the cytotoxic drug concentration and consequently the reduction of tumour size. In connection with the increased vascularization we investigated its use in age-related macular degeneration where it has demonstrated positive preclinical efficacy results, diabetic retinopathy and other ophthalmological indications. Two phase I trials have been completed and IPP-204106 is Phase II ready.

Metabolism and Diabetes

ImmuPharma's subsidiary 'Ureka' has initiated the development of a novel and innovative peptide technology platform through the collaboration with CNRS, gaining access to pioneering research centred on novel peptide drugs at the Institut Européen de Chimie et Biologie (IECB). Jointly, ImmuPharma and CNRS have filed a new co-owned patent controlling this breakthrough peptide technology. Ureka's current focus is in Diabetes Type II (GLP-1 analogues - once a month administration) and in Non-Alcoholic Steato-Hepatitis (NASH) where outstanding results have been obtained in validated pre-clinical experiments with peptide URK 614. There is also potential in cancer treatment (protein/protein interaction; P53 gene).