NM002 is a unique immunomodulator-antimicrobial that could bring about a paradigm shift in the treatment of inflammatory-infectious disease.
NM002 is a small molecule (aminothiol) derived from the innate immune defense response. It has the potential to resolve (hyper)inflammation as well as the infectious cause of that inflammation.
NM002’s unique combination of immunomodulatory (anti-inflammatory) and antimicrobial (antiviral and antibacterial) properties position this therapy candidate as a potential game-changer in inflammatory-infectious respiratory disease. NM002 is an intravenous (IV) medicinal candidate currently being investigated in a major international platform (phase 3) clinical study, REMAP CAP (A Randomised, Embedded, Multifactorial, Adaptive Platform trial for Community Acquired Pneumonia) for community acquired pneumonia (CAP). The first patients were enrolled and dosed in December 2021and the trial is ongoing. Study subjects are those in an intensive care setting with confirmed CAP of all causes (viral as well as bacterial, including COVID-19). Primary outcome measures of the phase 3 trial are all-cause mortality at day 90 and days alive and not receiving organ support in ICU for patients with suspected or proven COVID-19 infection.
Although NM002 is initially being developed in IV form, there is potential to investigate an oral form of NM002 for treatment of less severe CAP in hospital and community settings (see below re AMR).
NovaBiotics extensive research with, and deep understanding of aminothiol biochemistry and biology, cysteamine in particular, supports and de-risks NM002’s application in CAP. A compelling body of preclinical data concerning the immunomodulatory mechanisms of NM002, particularly targeting IL-6 and interferons, its host-directed antiviral effects and the company’s published work on cysteamine’s anti-virulence and antibiotic potentiating modalities are further augmented by positive clinical data for NovaBiotics’ NM001asset, derived from the same platform as NM002 and in late stage development for pulmonary exacerbations of cystic fibrosis (with planned expansion into non-CF bronchiectasis).
Antimicrobial Resistance (AMR)
In its capacity to potentiate antibiotic function and even ‘break’ antibiotic resistance (NovaBiotics published data) In addition to having anti-virulence and anti-biofilm properties, NM002 and NovaBiotics cysteamine platform could be part of the solution to a worsening AMR crisis. Put simply, NM002 and the immunology based platform from which it is derived ‘supercharges’ existing antibiotics and not just for CAP. This extends our platforms’ utility beyond respiratory disease to other conditions associated with drug-resistant or otherwise difficult to treat bacterial pathogens.
Healthcare Burden and Global Market
NM002 is currently being investigated as an intervention in Community Acquired Pneumonia (CAP) in the Phase 3 Global REMAP CAP platform clinical trial. Global deaths from CAP, a significant cause of global mortality, exceed 3 million cases annually. CAP is in fact, the leading cause of death in the developing world and the fourth most common cause of death world-wide. CAP is also the leading cause of hospitalisation from lung disease, with CAP severe enough to require admission to intensive care units associated with high mortality risk. CAP healthcare costs are in the range of $17 Bn annually in the US and €10 Bn in Europe, the vast majority of costs being for inpatient care. The global market for CAP therapies is growing at an 8.5% CAGR and estimated to reach $25.5 billion by 2030, driven in part by a continued increased prevalence of CAP.
A potential game changer in symptom-focused therapy for cystic fibrosis (CF) and non-cystic fibrosis bronchiectasis (NCFBE)
NM001 is a novel, highly differentiated therapy candidate in development for CF and NCFBE-associated lung disease. NM001 has a unique multi-action including anti-inflammatory effects, potent mucolytic action, antimicrobial, anti-virulence and antibiotic-potentiating effects.
NovaBiotics is developing two forms of NM001. Oral NM001 for pulmonary exacerbations of CF and NCFBE and inhaled NM001 for the maintenance of ventilatory function in CF and NCFBE patients. The application of the oral and inhaled forms of NM001 in exacerbating and stable patients respectively could provide the opportunity for a paradigm shift in standard of care therapy. Importantly, as a CF candidate therapy, NM001 is not a mutation-specific CFTR-targeting intervention. The unique multi-activity of NM001 has been demonstrated in our clinical trials and a range of laboratory experiments. Our NovaBiotics publications list contains links to articles and can be viewed by clicking here [opens in new window].
NM001 in oral (tablet) form recently completed an exploratory phase 2b global study (CARE CF 1) in CF patients following an earlier, positive phase 2a trial. CARE CF 1 was designed to determine which clinical endpoints are the most appropriate to demonstrate the benefits of NM001 in exacerbating (adult) CF patients who took NM001 alongside their other ‘standard’ medicines for 14 days (or placebo). CARE CF 1 was also designed to determine which dose(s) and treatment regimen(s) of NM001 is/are optimal for efficacy. The endpoint and dose(s) were successfully identified from CARE CF 1. We now plan to progress NM001’s development in registrational studies comprising both CF and NCFBE patient cohorts.
The inhaled (dry powder) formulation of NM001 has recently been optimised and from a platform of very encouraging preclinical efficacy and safety data, NovaBiotics is working towards initiating phase 1 clinical studies for inhaled NM001.
Orphan drug designation has been granted in the US and Europe for NM001 in the treatment of CF. NM001 gained Fast Track Designation in the US in 2018. Oral NM001 was designated as a priority review medicine by the Central European Health Technology Assessment body in July 2019.
Healthcare Burden and Global Market
NM001 is currently being investigated as an adjunct therapy for the treatment of infectious pulmonary exacerbations (PEx) in cystic fibrosis. NM001 is an antibiotic potentiator and anti-virulence agent with mucolytic properties and can reduce inflammatory markers (e.g. CRP) in PEx. NM001 is unique in the market being mutation agnostic and targeting symptomology of CF respiratory disease. The combined market for oral and inhaled therapies in CF is £32 billion. There is significant cross-over in phenotype between CF and NCFBE and there were an estimated 1.5 million cases of NCFBE in the 7 major markets in 2020. The NCFBE is much larger potential therapeutics market than CF, though it is still underserved, and incidence is age-related and increasing in the major markets (US annual growth rate is 8% since 2001). The NCFBE therapeutics market is set to rise at 27.1% CAGR between 2018-2030.
NovaBiotics’ peptide candidate NP339 is in development for the prevention and treatment of life-threatening and life-limiting diseases that can result from compromised immunity
Life-threatening fungal infection in immunocompromised patients
Patients with compromised immunity lack critical endogenous defense systems with protect them against potentially life-threatening fungal infections.
NP339 has been designed to temporarily restore these defenses. It is an antifungal peptide with rapid, fungicidal activity against a broad range of clinically relevant pathogens including Aspergillus spp, Candida spp, as well as emerging and drug-resistant organisms such as Mucorales and Candida auris. NP339 has a resistance-mitigating mechanism of action and toxicity profile that is highly distinct from other classes of antifungal because it is based on immune defense molecules. NP339 is being developed in intravenous form for hospital use for the prevention and treatment of invasive disease in immunocompromised patients including those undergoing cancer therapy and stem cell transplant.
Our peer reviewed article ‘Preliminary Characterisation of NP339, a Novel Polyarginine Peptide with Broad Antifungal Activity’ can be viewed here [opens in new window]
Life-limiting & Life-threatening infection of the airways in patients with respiratory disease
Fungal infections of the airways are an increasing clinical challenge and negatively impact outcomes in patients with complex respiratory disease.
NP339 is an antifungal peptide with activity against Aspergillus spp. Scedosporium spp., Exophiala spp. and other pathogens of relevance to respiratory disease and is being developed in inhaled form for chronic and acute treatment of respiratory fungal infections. The physicochemical properties of NP339 are ideally suited for direct delivery into the lungs and in simulations of respiratory Aspergillus fumigatus infection, we have already demonstrated that inhaled NP339 is effective in killing Aspergillus within lung tissue. See ECCMID poster here [opens in new window].
Healthcare Burden and Global Market
It is estimated that fungi are responsible for 13 MM infections per year globally while also contributing to 1.5 MM deaths annually. More recent analyses in US shows 7.2 MM cases of fungal disease in 2018 with a concomitant associated mortality of 4.9 %. Fungal diseases cost health care providers $55,000 per patient on average with costs associated with invasive infections exceeding $100,000 per patient. There is a significant healthcare and socioeconomic burden of fungal infection and with rising susceptible patient populations, is forecast to grow. The economic burden of fungal diseases in the US was $11.5 Bn in 2019 with $4.5 Bn attributed to diseases Aspergillosis and Candidiasis. the global market for antifungal therapies is predicted to be circa $20 billion by 2027, with at least $14 Bn attributed to therapies for invasive fungal disease.
The first, rapid-acting solution for nail disorders which is based on the nail’s natural defence mechanisms
NP213 is a novel peptide, generated from NovaBiotics’ proprietary technology platform.
NP213 is based on the natural peptides present within nails and skin and which play a crucial role in maintaining healthy tissue.
Clinical & laboratory studies have demonstrated that Novexatin®, a brush-on (topical) formulation containing NP213 is safe, well-tolerated and effective in resolving nail disorders following just one month of once-daily application. Novexatin® works to rapidly restore nail health, improving condition and appearance (within days as reported by users in a clinical study) by hydrating the nail and mimicking the body’s peptide defence system.
Healthcare Burden and Global Market
Nail disorders are estimated to affect up to 12% of the world’s population and treatments for these conditions represent a growing global market estimated to reach $10 billion by 2032. There are a number of environmental and medical factors associated with nail disorders including physical insult to the nail, infection, increased age, poor circulation, compromised immunity and diabetes.
Targeting a breakthrough against drug resistant bacterial infections
NP432 has been derived from a platform of antibacterial peptide therapy candidates. These bactericidal agents have a number of key benefits over conventional antibiotic therapies and the clear potential to succeed where existing treatments for a number of bacterial infections, including drug resistant MDR and XDR infections are failing.
NP432 and our family of antibacterial peptides are derived from same technology platform as NP213 (Novexatin) and NP339 and so the route to clinic anticipated for this novel antibacterial therapy candidate has already been significantly de-risked.
NP432 is NovaBiotics’ preclinical stage lead antibacterial peptide asset and along with its family of related peptides is broad-spectrum, potently and rapidly bactericidal in vitro against clinically and economically important bacteria. NP432 is active against bacteria identified by the World Health Organisation as Priority Pathogens including Pseudomonas aeruginosa, Clostridium difficile, Acinetobacter baumannii and Klebsiella pnuemoniae. NP432 and its related family of antibacterial peptides are active against drug resistant and multi drug resistant bacteria. NP432 has shown to be well-tolerated and has demonstrated efficacy in in vivo infection models.
NP432’s unique therapeutic mechanism of action is rapid bacterial membrane perturbation and lysis leading to bacterial death (not merely inhibiting growth). Importantly, this mechanism of action also means that NP432 does not interact with human cells and that is possesses no or a very low risk of acquired resistance developing in the bacteria it targets compared to conventional antibiotics.
Healthcare Burden and Global Market
Drug resistant bacterial infections were directly responsible for 1.27 million global deaths in 2019 and associated with 4.95 million deaths the same year. The healthcare and socioeconomic burden of bacterial infection is significant and will only continue to grow. The global market for antibacterial therapies is estimated to reach $20 billion by 2027. NovaBiotics is pioneering novel, immune based approaches to tackling difficult-to-treat, potentially life-threatening bacterial infections with its peptide NP432 technology. Uniquely, NP432 effectively kills antibiotic sensitive and resistant bacteria both in planktonic, biofilm and persister cell form.
A novel strategy for the topical treatment of dermatological conditions
NP108 is a peptide antimicrobial specifically designed for topical use in bacterial and polymicrobial dermatological conditions. NP108 is rapidly microbicidal against a number of organisms including Staphylococcus spp (including MRSA and mupirocin-methicillin-resistant SA) and Propionibacterium acnes. NP108 also has activity against Malassezia spp.
NP108 has potential for application in Rx but also consumer focused products targeting skin, scalp, wound and personal care as well as in nasal decolonisation of MRSA/MMRSA [NP108 AAC Paper opens in new window]. We have generated a compelling preclinical data set demonstrating NP108’s microbicidal activity, in vitro cytotoxicity/haemolysis profile and resistance-agnostic and resistance-mitigating mechanism.
NP108, as per NovaBiotics’ other peptide candidates, is a synthetic, ‘re-engineered’ version of the innate immune defence molecules that provide one of the first lines of defence within the skin. Our rationale to deploy NP108 as a ‘supercharged’ peptide for topical use is to bolster dermal and mucocutaneous defences and intervene in superficial dermatological conditions associated with specific microbes, using an immune based Vs antibiotic approach.