Phase 2a Clinical Trial – A new and effective inhaled antibiotic treatment for Cystic Fibrosis lung infection

Project Duration – 1 Year

Boosting the power of antibiotics in Cystic Fibrosis

Associate Professor Barry Clements and the team at Respirion Pharmaceuticals are developing a new inhaled combination treatment that comprises the antibiotic tobramycin with an added booster that increases the antibiotic’s power to kill resistant bacteria and reduce inflammation. The treatment is currently in Phase 1 clinical trials in Australia and the USA to determine the most effective dose.  We are excited to join the CF Foundation (USA) as funders of this work.

Cure4CF’s funding will support 18 Australian people with CF to be part of the next, and important, Phase 2 phase of the clinical trial where Associate Professor Clements’ team will investigate the ability of their combination therapy to:

1. Improve bacterial clearance from patients with Cystic Fibrosis (CF)
2. Demonstrate safety and tolerability of the combination therapy in a larger CF cohort
3. Investigate how the combined therapy reduced inflammation
4. Evaluate the experience of CF patients who have participated in the trial

Why are antibiotic boosters needed?

Bacterial infections remain a significant challenge for people with CF, even in those whose health has been improved by modulator therapy.  Repeated infections along with significant antibiotic resistance often mean long-term treatment, many side effects and low success rates.  In recent research from the UK, intravenous antibiotic therapy for more than a year could not resolve Pseudomonas aeruginosa infections in around half of the people studied.  This highlights the urgent need for new strategies to better combat infections.

Why macrophages?

In the 2023 Australian CF Data Registry Report, 43% of adults with CF had a positive sample for Pseudomonas aeruginosa and more than 25% of adults and 14% of children take regular inhaled antibiotics. Pseudomonas and other bacteria are difficult to eradicate, often resistant to antibiotics, and can permanently colonise the CF lung. With the increasing failure of existing antibiotics and no new antibiotics to treat resistant respiratory infections approved for more than 15 years, Associate Professor Clements and his team were inspired to develop their booster RSP-1052.

Emerging evidence shows that modulator therapy alone is not sufficient to eradicate bacteria that have colonised the lung. Increased dosing with ineffective currently available antibiotic therapy simply increases side effects and adds to the treatment burden without reducing the disease burden.

The potential of booster treatments is an emerging research area.  Associate Professor Clements initially studied this booster in a group of 22 people with CF and found that after six weeks there was increased clearance of bacteria and an improvement in lung function compared with antibiotic treatment alone. The combination therapy was well tolerated and safe.

What is unique about this project?

The team at Respirion Pharmaceuticals has worked with CF patients to guide the formulation of the new treatment.  One important improvement has been switching to the use of the new mesh nebuliser which delivers each dose of combination therapy in less than 10 minutes, instead of around 30 minutes with current nebulizers. This means a saving of up to 40 minutes a day for their twice daily antibiotic treatment.

In laboratory experiments the combination treatment has shown to be able to boost the antibiotic’s ability to kill resistant bacteria by more than 1000 times. This is achieved by removing important nutrients from the lung environment that would otherwise help the bacteria to withstand antibiotic activity.

This study aims to demonstrate improved bacterial clearance and lung function and reduced inflammation and exacerbations.  With a faster delivery time, treatment burden for people with CF will also be reduced.

What will be the pathway to moving this therapy into the clinic?

Excitingly, Cure4CF’s funding for an additional 18 Australian CF patients to participate in the study,  will increase the chances of demonstrating clinical efficacy. In turn, this will support progression of the development program to the next phase of clinical trials on the path to approval from the USA Food and Drug Administration and the Australian Therapeutic Goods Administration for the product to be licensed in both countries.

About The Team

Founded in 2018, Respirion Pharmaceuticals is an early-stage biotechnology company focused on developing new treatments for respiratory disease. The Company is a spinout from the Telethon Kids Institute in Perth where the product development was incubated. The Company has partnered with Australia’s largest life science investment fund, the Medical Research Commercialisation Fund, and the US Cystic Fibrosis Foundation to conduct further clinical trials in Australia and the US.

Associate Professor Barry Clements trained and researched in Respiratory medicine at the Royal Brompton Hospital, London before returning to Perth where for the last 35 years he has been Clinical Consultant in Respiratory Medicine and Cystic Fibrosis at Perth Children’s Hospital (formerly Princess Margaret Hospital). Prof Clements’s frustration with the limited capacity of current treatments to help CF children in their daily struggle with their disease stimulated his interest in researching new and more effective treatments, focusing on improving both respiratory drug delivery and inhaled antibiotic efficiency.

Simon’s Project

Simon lives with a rare CF gene preventing him from using current CF medications. As a result, he needs alternative treatments to combat the harmful bacteria that damage his young lungs.

Simon’s parents Harry and Teresa Bazouni, started the Team Simon Foundation in the hope of raising funds for research into a cure for CF. To date they have raised an incredible $1.5M and are major contributors to our research funding program. This project is dedicated to Simon, his family and their amazing supporters.