Novel immunotherapy targets periodontal disease

Denteric is developing an immunotherapy that targets the bacterium causing severe periodontal (gum) disease, offering hope to the one billion people worldwide suffering from this chronic and painful condition that increases the risk of serious health complications.

The need

Periodontal disease affects approximately one in three adults globally, and more than 50 per cent of Australians over the age of 65. The bacterium Porphyromonas gingivalis, which causes severe forms of the disease, is particularly adept at evading the immune system, residing in a pocket between the gum and the tooth root. In extreme cases, the infection destroys the tissues anchoring the teeth, leading to tooth loss, associated stigma, and mental health impacts.

“There is currently no long-term cure for people who suffer from severe periodontal disease,” Denteric Founder Professor Eric Reynolds said. “Treatment typically involves the painful scraping of the roots of the teeth below the gum line and may also include the use of antibiotics, which often fail to work and can contribute to antimicrobial resistance.”

Severe periodontal disease also increases the risk of heart attacks and strokes by two to three times and is associated with other chronic conditions including Alzheimer’s, diabetes, rheumatoid arthritis, and certain cancers. The economic burden of the disease is staggering – estimated at US$186 billion in direct costs and US$142 billion in indirect costs in 2019 alone.

The research

The journey to develop an effective therapy began more than 20 years ago in Professor Reynolds’ laboratory at the University of Melbourne. As CEO and Director of Research of the Oral Health CRC (2009-2018) – a collaboration between the University, Mondelez International AMEA, GC Corporation, and CSL Limited (CSL) – Professor Reynolds led research focused on reducing the burden of oral diseases on the Australian population.

Key researchers in this decades-long effort included Professor Neil O’Brien-Simpson from the University of Melbourne, and senior staff from CSL, including Dr Andrew Nash and Dr Tony Rowe. Their research showed that an immunotherapy approach could prevent the bacterium from causing bone and tissue destruction. “After years of laboratory work, we discovered that by targeting specific components of the bacterium, we could potentially train the immune system to neutralise these bacteria and stop bone loss and gum destruction,” Professor Reynolds said.

Going to market

In May 2019, Denteric was established to progress the research and manufacturing processes needed to develop GPV381, a recombinant protein subunit therapy currently in clinical trials. With Brandon Capital leading an initial investment round of $14 million – supported by CSL and the University of Melbourne – Denteric gained the necessary funding to advance from laboratory research to human trials.

“The University of Melbourne and CSL contributed the foundational intellectual property and expertise developed within the CRC. In addition, the University has provided access to Denteric is developing therapies that target the major virulence factors produced by the bacterium Porphyromonas gingivalis. Their primary goal is to provide options to treat and prevent severe periodontal disease, a chronic and painful condition associated with serious health complications. technology platforms and facilities, and remains a key shareholder and investor,” Professor Reynolds said. A dedicated research laboratory has also been set up at the Jumar Bioincubator.

Denteric Chief Operating Officer (COO) Larisa Chisholm said establishing a dedicated company run by professionals with experience in translational drug development and commercial vaccine strategy was essential for attracting the necessary funding and giving the technology the highest probability of success.

“Without the support of the University, CSL and Brandon Capital, the research could never have advanced to human clinical testing,” Ms Chisholm said.

The impact

In just five years, Denteric has secured additional Australian Government funding to expand its research horizons, including a $500,000 CUREator grant to explore GPV381’s potential to prevent Alzheimer’s disease pathology in mice, and $1.2M in CRC-P funding for an mRNA proof-of-concept study. A total of $25M has now been committed to the company by its Series A shareholders.

Denteric reached a significant milestone in January 2024, with the first clinical trial participants receiving the GPV381 immunotherapy. This Phase I trial has now concluded, demonstrating that the immunotherapy is safe and well tolerated.

“It was an incredibly moving moment to see years of work finally reach participants in the clinic,” Ms Chisholm said.

“Now, the entire team looks forward to the next phase – the dosing of the first patients with severe disease, hopefully in the second half of 2025.”

The company is also looking to raise its Series B funding on the back of the Phase I trial data.