Neumifil

About Neumifil

Designed to inhibit viral entry through the epithelium of the nose, preventing virus-induced exacerbations of underlying respiratory  diseases.

Neumifil is a self-administered, easy to use, intranasal spray developed from our proprietary GlycoTarge™ platform. The spray is locally acting to inhibit viral entry through the nose, blocking and preventing viruses from gaining entry into the host.

Neumifil is a novel, engineered multivalent Carbohydrate Binding Module (mCBM40), which is being developed to offer at-risk patients, suffering from chronic pulmonary diseases, protection from viral induced exacerbations of their underlying respiratory diseases. With its unique mechanism of action, Neumifil potentially offers reduced susceptibility of the virus developing resistance to the medication, such as that observed to develop against directly acting anti-virals or vaccines.

Neumifil science

Neumifil, is a multivalent, sialic acid-binding protein engineered from the Carbohydrate-Binding Module (CBM) of streptococcus pneumoniae neuraminidase A protein (SpCBM). Multivalency with respect to sialic acid-binding is achieved by fusing two tandemly linked SpCBM domains to an oligomerization domain, derived from Pseudomonas aeruginosa sialidase, that self-associates to form a trimer.

By directly targeting sialic acids on host cells in the nose, Neumifil blocks viral entry to cells and the establishment of infection.

Given this novel host-targeted mechanism of action, Neumifil has reduced the potential for the development of drug resistance developing in the viruses.

For viruses bearing surface glycoproteins including SARS-CoV-2, Neumifil has a second mechanism of action that can prevent viral entry.  In addition to blocking the sialic acid containing cellular receptor, Neumifil can also bind to viral protein glycans with high affinity, preventing entry to the host cell.

A gene coding for a single sialic acid binding module is derived from a gene encoding a Streptococcus pneumoniae neuraminidase (NanA). Two of these genes are tandemly-linked using DNA coding for a short connecting peptide. This gene is then linked to a gene that codes for a small protein domain which forms a trimer in a Psuedomonas aeuriginosa sialidase. When expressed in E. coli, the trimerisation domains self-associate creating a protein with six sialic acid binding domains. The affinity for sialic acid increases several thousand-fold when going from the monomer to the hexamer.

Programmes

Preclinical data

In multiple animal studies, Neumifil demonstrated an excellent safety profile and broad efficacy against a wide range of respiratory viral pathogens, including Influenza Virus (IFV), Respiratory Syncytial Virus (RSV), and Coronavirus, including SARS-CoV-2.

Neumifil has demonstrated high-affinity binding to cellular sialic acids and/or virus proteins (e.g., the spike proteins of multiple SARS-CoV-2 strains) and can effectively prevent cell entry and infection in in-vitro assays. When administered prophylactically or therapeutically in-vivo, Neumifil has significantly improved animal clinical outcomes and demonstrated protection against virus-challenge in multiple animal models.

Clinical data

Positive top line results from Phase 1 data

Pneumagen undertook a first-in-human, placebo (vehicle) controlled, single ascending dose; multiple ascending dose study of Neumifil in healthy volunteers.  A total of 60 participants were recruited.  Single dose and multiple doses (daily dosing for seven days) were administered to the study participants.  The study was designed to assess the safety and tolerability of Neumifil.  Safety was assessed between each dose cohort.

Systemic exposure of Neumifil and effect of Neumifil on cytokine concentrations were also assessed.

The study demonstrated:

• Single and repeated intranasal doses of Neumifil were safe and well-tolerated in healthy volunteers.
• There were no clinically significant findings or changes in clinical laboratory variables, the results of nasal and physical examinations, vital signs, or ECGs, during the study.
• Neumifil was not detected in any of the blood samples collected, indicating systemic exposure does not occur or the concentrations are undetectable.

More information can be found at https://www.clinicaltrials.gov/ct2/show/NCT05093530?term=pneumagen&draw=2&rank=2

Next steps – Phase 2

Neumifil is now being assessed for efficacy in a controlled human infection model (CHIM) study due to complete in mid-2023.  This is a Phase 2a, randomised, double-blinded, placebo-controlled study conducted at a single centre.

A total of 100 participants will be recruited into this study.  Participants will receive 0, 1 or 3 doses of Neumifil by an intra-nasal spray, prior to being challenged with an infective dose of the H3N2 strain of influenza virus.  This clinical proof of concept study has the reduction of the incidence of symptomatic influenza infection and the reduction of the severity of symptoms as the primary endpoints, thus assessing the efficacy of Neumifil, to provide an early treatment or prophylaxis option for at-risk patients. Secondary endpoints include an evaluation of the reduction or shortening of viral shedding and reduction of nasal discharge.

(https://www.clinicaltrials.gov/ct2/show/NCT05507567?term=pneumagen&draw=2&rank=1)

Pneumagen is planning a Phase 2b study in patients planned to begin in early 2024. This will be an international multi-centre placebo controlled trial looking at exacerbation frequency in patients with COPD. The clinical study is being designed in close collaboration with Pneumagen’s Clinical Advisory Group.

Market opportunity

There is a significant medical need for the prevention and treatment of virally induced exacerbations in patients with underlying respiratory diseases such as COPD, as well as for patients who have weakened immune systems including the elderly and immunocompromised.

The exacerbation of disease caused by respiratory viral infections can accelerate lung function decline and lead to greater morbidity and mortality rates as well as significantly higher healthcare costs.

Neumifil is being developed to and thereby the disease burden for patients who currently have limited prevention options.

The shortcomings of current treatments

Corticosteroids (inhaled and oral) are commonly prescribed in the management of asthma and COPD patients by reducing inflammation. However, common side effects of oral steroids include, weight gain, indigestion, insomnia, feeling  restless, sweating a lot and mild mood changes. Serious long term effects include, diabetes, adrenal gland suppression, hypertension and glaucoma. Inhaled steroids can result in oral thrush and hoarseness.

For those patients that have frequent exacerbations, prophylactic antibiotics are administered to help reduce the frequency of exacerbations and admissions to hospital. However, antibiotics will have limited treatment efficacy for viral respiratory tract infections, can lead to antimicrobial resistance and are used at a considerable cost to payors.

Overall, there are no current drugs on the market that address the stopping of the virus in the nasal passages, with the potential to result in a significant reduction of exacerbations.

Neumifil addresses a significant unmet need

The National Institute of Clinical Excellence estimate 1 in 8 emergency admissions to hospital in the UK are for COPD (130,000 per year). Many more experience exacerbations that do not require hospitalisation. The US COPD foundation estimate 30 million Americans are affected by COPD. A paper reported 1.2 million hospitalisations in the USA in 2006. An exacerbation means further exacerbations are more likely leading to increased morbidity and health care utilisation.

Exacerbations not only affect the quality of life at the time of exacerbation they contribute to declining lung function.