NP339

For the front-line treatment of medically unmet, mould and yeast infections.

 

NP339 is an antifungal peptide with potent, rapid ‘kill’ activity against a broad range of clinically relevant moulds and yeasts including Aspergillus spp., Candida spp., Cyptococcus spp. as well as emerging fungal pathogens such as Scedosporium spp., Exophiala spp. and the Mucorales.

Invasive Fungal Disease (IFD)

NP339 is a preclinical drug candidate being developed under a £1.8m Small Business Research Innovation contract from the UK’s Department of Health & Social Care (see article here) as an intravenous therapy for life threatening invasive fungal disease (bloodstream and deep tissue fungal infections) including those caused by yeasts and moulds that are resistant to existing antifungal therapies.

Cystic Fibrosis & Allergic Bronchial Pulmonary Aspergillosis

An inhaled form of NP339 is under development in our laboratory for delivery directly into the airways in patients with, or at risk of fungal infections of the lungs and airways. The respiratory tract is the primary route of entry/source of mould infections which can later become disseminated and switch to IFD under circumstances where the body’s immune system is compromised. An inhaled form of NP339 that can act locally within the lungs could be of significant benefit not only in IFD but in a number of now increasingly common, chronic conditions such as Allergic bronchopulmonary aspergillosis (ABPA), a severe allergic reaction of the respiratory track to Aspergillus that is becoming more common, particularly in patients with long term chest conditions such as asthma.

The chemical properties of NP339 make it ideally suited for direct delivery into the lungs and in simulations of lung Aspergillus fumigatus infection, we have already demonstrated that inhaled NP339 is very effective in killing Aspergillus within lung tissue [see ECCMID poster here].

ABPA is also increasingly common, and a significant impact on quality of life, in patients with cystic fibrosis (CF). Aspergillus infection also precludes CF patients from lung transplant because of risk of IFD developing post-surgery with immunosuppression. Inhaled NP339 therefore complements our Lynovex programme in addressing unmet infections of the airways in CF. Other respiratory fungal infections are on the increase in CF patients, including those caused by Scedosporium spp and Exophiala spp. These infections are very difficult to treat and can have significant impact on morbidity and mortality in a proportion of CF patients. NP339 is potently active against all of these CF-relevant fungal pathogens and an inhaled form of this peptide could meet a clear and now more urgent clinical need; the new ‘CFTR modulator’ therapies interact with existing classes of commonly used (azole) antifungals and so CF patients cannot use both treatments together without risk of potential side effects.

Oral-Pharyngeal Candidiasis

Infections of the mouth and throat (oral cavity and pharynx) with Candida spp yeast are very likely to occur in individuals with a suppressed immune system.  This can be due to an underlying illness, the effects of chemotherapy and immunosuppressant medication including steroids.  Oral pharyngeal Candida (OPC) can have a very significant impact on the quality of life of those affected, particularly on top of the illness or treatment which led to the infection.  OPC can be painful and eating becomes a challenge or not least, unpleasurable because of OPC’s impact on taste.  Current antifungal therapies for OPC, taken as tablets or mouthwash, are notoriously ineffective.  Added to this, drug-drug interactions and resultant side effects of azole antifungal therapy with medications such as statins means many individuals affected with OPC cannot be given take systemic antifungal treatments. We have developed NP339 in formulations for use directly in the mouth and throat as effective, rapid acting and pleasant to use treatments for OPC.

IFD Key Facts

  • An increasingly urgent unmet medical problem ‘over-shadowed’ by bacterial resistance
  • 2,000,000 million deaths worldwide annually caused by Invasive fungal disease (IFD)
  • Aspergillus spp., rare moulds & emerging, drug resistant Candida infections are the most clinically challenging forms of these life-threatening infections and now account for more deaths than malaria or tuberculosis
  • Mortality rates for Aspergillus infections are as high as 80% (100% without treatment)
  • Candida remains the most common cause (over 50%) of hospital based IFD
  • Only 3 existing classes of antifungal in mainstream clinical use versus 14 classes of antibacterials
  • Direct healthcare costs for IFD are as much as £83,000 per patient
  • The Global Invasive Fungal Infection Market was valued at $6.1 billion in 2018

A Unique Proposition in Next Generation Antifungal Therapy

  • NP339 is a synthetic 2kDa cationic peptide;
  • Derived from NovaBiotics’ proprietary antimicrobial peptide (AMP) technology platform;
  • Engineered from, and closely related to, the body’s natural, infection-fighting AMP;
  • NP339 targets the fungal membrane and kills fungi by disruption and lysis of the cell and;
  • Because this mechanism of action is specific only to fungal cells, NP339 is not toxic to human cells – a major issue with existing antifungal classes;
  • NP339 rapidly kills (faster than conventional classes of antifungal drugs) metabolically active and inactive fungi and also spores.