Late-breaking Abstract by BiomX Inc., a company developing novel natural and engineered phage therapies targeting specific pathogenic bacteria, presented data from Part 1 of its ongoing Phase Ib/IIa (NCT05010577) study to evaluate BX004, a new phage product candidate, for the treatment of chronic Pseudomonas aeruginosa (PsA) lung infection in patients with cystic fibrosis at the 2023 International Congress of the European Respiratory Society (ERS).

Cystic fibrosis (CF) is caused by mutations in the CFTR gene that encodes a protein that helps regulate the movement of salt and water in and out of the cells. In people with CF, proteins do not work well, causing thick, sticky mucus to build up, eventually blocking the airways and creating a breeding ground for bacteria and other germs to grow and thrive. Pseudomonas aeruginosa (PsA) can also make it harder for the immune system to clear the infection independently due to forming a biofilm in the patient’s lungs. Of the infected patients, a vast majority of them succumb to respiratory failure due to chronic inflammation and infection. Pseudomonas aeruginosa and chronic PSA infection are associated with a progressive decline in lung function. Removing and treating this organism from the CF airway poses a tough challenge for CF care providers.

Treating Pseudomonas aeruginosa infection with antibiotics is difficult because biofilms are a protective coating that keeps antibiotics away. They can also undergo changes that allow them to become resistant over time. Despite new treatments directed against CFTR, CF patients continue to suffer from persistent and incurable infections, such as those caused by Pseudomonas aeruginosa, and there is a clear need for new treatment approaches to plunge in.

Bacteriophages have been proposed as an alternative to antibiotics, potentially providing highly selective activity against pathogens. All hopes that bacteriophages can be a new treatment strategy against drug-resistant bacterial infections have been bolstered by a study conducted by BiomX in patients with cystic fibrosis (CF). Based on the BOLT (Bacteriophage Lead to Treatment) platform, BX-004 is under development for treating cystic fibrosis and resistant Pseudomonas aeruginosa infections, administered as an inhalational formulation.

In the trial, preliminary evidence of efficacy in patients treated with BX004 was comprehended despite the small sample size and short treatment duration. The recorded results to date showed that in patients with cystic fibrosis and chronic Pseudomonas aeruginosa infection, the bacterial load – measured in colony forming units (CFU) on Day 15 – decreased fivefold – in the first placebo-controlled trial of bacterial mixture BX004. At Day 15, the mean P. aeruginosa burden was reduced by 1.42 log10 CFU/g compared to 0.28 log10 CFU/g in those receiving placebo.

The Phase I results of the Phase Ib/IIa clinical trial (NCT05010577) study were impressive, demonstrating efficacy within a short treatment duration of 7 days and the safety and tolerability of BX004 demonstrating short-term and incremental treatment regimens.

BiomX recently completed patient screening in Part 2 of the ongoing Phase Ib/IIa trial, with patient enrollment expected to exceed initial estimates, reflecting the growing awareness of the BX004 program within the CF patient community. Adding to the virtuous progress, BX004 has also received Fast Track Designation from the US FDA, confirming the BX004 program’s potential to treat CF’s most serious and challenging unmet medical needs.

There are no approved treatments based on bacteriophages except for some experimental ones. If approved, the CF paradigm will have an altogether novel and important treatment in its bucket. In all prospects, approving a treatment like this will be a cutting edge alongside creating a huge market. With established therapies, including SYMDEKO, ORKAMBI, KALYDECO, AND TRIKAFTA, BX004 is yet to prove its game.

Based on DelveInsight’s “Cystic Fibrosis – Market Insight, Epidemiology And Market Forecast – 2032, the CF market in 2022 was estimated to be approximately USD 5 billion in the United States against a patient population of 37,354, which is likely to surge at a considerable CAGR during the forecast period.