Hamlet Pharma

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