Lynovex™ Technology Summary

Prevention of Biofilm formation

NovaBiotics mucoactive agent Lynovex® (NM001/Cysteamine) demonstrated total inhibition of biofilm formation by P. aeruginosa in microfluidic flow cell system (Figure 2). Lynovex® performed better than any of the controls tested at the same concentrations, including the active components of the gold standard mucolytic agents, Domase Alfa (DNAseI) and Mucomyst (N-acetyl-cysteine).

Figure 2. Prevention of P. aeuroginosa (strain ATCC BAA-47) biofilm formation by NovaBiotics mucoactive agent Lynovex® in a Bioflux microfluidic channel in vitro system.

Safety and Toxicity

Lynovex® is a disulfide bond disrupter already approved for other therapeutic applications and passed successfully the regulatory process to reach marketing approval, which will enable fast-track development of this compound for the treatment of the infections associated with the orphan disease cystic fibrosis.

Lynovex® is very well tolerated in an in vivo model of respiratory Pseuodomonas infection and reduced lung tissue burden with one nebulised dose.

Resistance Development and Post-Antimicrobial Effect

Resistance of representative Gram-negative and Gram-positive bacteria to Lynovex® (NM001/Cysteamine) and NovaBiotics cAMPs has not been observed in vitro after multiple passages.

A direct comparison of the antibiofilm activity of Lynovex® (NM001/Cysteamine) and N-acetylcysteine (Mucomyst), alone and in combination with tobramycin, was carried out and the metabolic activity of the biofilms was determined post-treatment to identify the post-antimicrobial effect of these compounds. The data provide clear evidence of the antibiofilm activity of Lynovex® (NM001/Cysteamine), alone and in combination with tobramycin, with a significant post-antimicrobial effect (Figure 3) as demonstrated by the delayed bacterial growth and reduced metabolic activity of the biofilm following treatment.

Novel mucolytic agent for application against bacterial biofilms
Uniquely, Lynovex® shows antibacterial activity, which differentiates it from other mucoactive agents
Lynovex® is already approved for other non-related therapeutic uses i.e. already proven as being safe
Lynovex® demonstrates:
- antimicrobial activity against both Gram-negative and Gram-positive bacteria
- prevention of biofilm formation
- disruption of established biofilms
- efficacy against both metabolically active and inactive bacteria, e.g. persister cells
- a low potential for resistance development due to direct physical interaction with cell membranes
- additive/synergistic activity with conventional antibiotics
- delivered directly to the respiratory tract by inhalation (nebulisation)

Spectrum of Activity
Lynovex® shows anti-biofilm and antibacterial activity against both Gram-negative and Gram-positive bacteria (Table 1). Lynovex® retains bactericidal activity at physiologically-relevant pH and salt concentrations against a broad range of type strains and clinical isolates obtained from cystic fibrosis patients and other bacterial infections.

Table 1. Broad-spectrum antimicrobial activity of Lynovex® against representative Gram-negative and Gram-positive bacterial strains. The MICs are shown in µg/ml.

Combinations

Lynovex® shows additive and synergistic activity with NovaBiotics AMPs (Table 2) and conventional antibiotics commonly used for the treatment of respiratory and dermal infections. Lynovex® can potentiate the activity of Tobramycin against Burkholderia cepacia (Figure 1).

Lynovex in combination

Table 2. Additive and synergistic activity of Lynovex® in combination with conventional antibiotics.

lynovex in combination graph

Figure 1. Lynovex® can potentiate the activity of Tobramycin against Burkholderia cepacia.