Hamlet BioPharma, the pharmaceutical company, specializing in the development of drugs for cancer and infections, today announces progress in Tuberculosis therapy. The group led by Professor Gabriela Godaly, has conducted a study on the antimicrobial peptide NZ2114, which has been accepted for publication in Frontiers in Microbiology.

The key findings are summarised below:

• The study highlights NZ2114, a plectasin variant, as a promising candidate therapeutic against Mycobacterium tuberculosis, capable of overcoming the bacterium's uniquely complex, lipid-rich, and low-permeability membrane.

• NZ2114 demonstrates potent antimycobacterial activity, synergizes with first-line TB drugs, remains stable in serum, and is non-toxic to human cells, making it a strong candidate for future TB treatment strategies.

• The antimicrobial effect was also observed against several clinical isolates of Gram-positive bacteria, including Enterococcus faecalis, Enterococcus faecium, and Methicillin-Resistant Staphylococcus aureus (MRSA).

• The peptide eliminated M. tuberculosis in a murine TB infection model with a log reduction of 81.14%) after three doses, compared to untreated controls.

Progress in tuberculosis therapy

Mycobacteria have a unique, lipid-rich membrane with low drug permeability, distinguishing them from other bacteria. This tri-layered structure is vital for their growth, virulence, and resistance to antibiotics. We previously identified a plectasin variant, NZX, which showed bactericidal activity against Mycobacterium tuberculosis, including multi-drug resistant strains, in several murine infection models.

This study investigated another plectasin variant, NZ2114, known for its effectiveness against Gram-positive bacteria, as a potential anti-mycobacterial peptide both in cells and disease models. NZ2114 effectively killed mycobacteria at a minimal inhibitory concentration (MIC₉₉) of 6.1 μM, was non-toxic to primary human cells, and remained resistant to serum degradation while preserving its antimycobacterial capacity. In a checkerboard assay, NZ2114 demonstrated synergy with the first-line TB drugs isoniazid and ethambutol.

The antimicrobial effect was also observed against several clinical isolates of Gram-positive bacteria, including Enterococcus faecalis, Enterococcus faecium, and Methicillin-Resistant Staphylococcus aureus (MRSA).

In our murine TB infection model, NZ2114 reduced M. tuberculosis by 81% after three doses. These studies suggest NZ2114 as a potential TB therapy, aiding in the control of this significant infectious disease.

For further information, please contact

Gabriela Godaly, Chair of the Board, Hamlet BioPharma AB, +46 733 38 13 44,

gabriela.godaly@med.lu.se

Catharina Svanborg, CEO, Hamlet BioPharma AB, +46 709 42 65 49,

catharina.svanborg@hamletpharma.com