Immune tolerance technology first to target cause of rheumatoid arthritis

An innovative immune tolerance technology, the first to target the underlying cause of autoimmune disease rather than treat its inflammatory symptoms, has entered first-in-human clinical trials.

The trial brings hope to patients with rheumatoid arthritis and has the potential to drive new therapeutics to other autoimmune diseases.

A research collaboration with US-based Janssen Biotech, Inc. supported the translation of the antigen specific immune tolerance induction (ASITI) technology as a treatment for rheumatoid arthritis through to the end of a first-in-human clinical trial.

The outcomes of the research collaboration and clinical development program and the application of the ASITI technology as a treatment for various autoimmune diseases is available for partnering from UniQuest.

Innovation

Only rheumatoid arthritis sufferers can appreciate the debilitating effects of this painful autoimmune disease. With the commercialisation support of UniQuest, a research team from The University of Queensland’s Diamantina Institute is pioneering an innovative rheumatoid arthritis therapy that offers hope to an estimated 23 million sufferers worldwide.

The team, led by Professor Ranjeny Thomas, discovered the body’s immune response could be “re-educated” to turn-off, rather than react to a self-antigen responsible for an autoimmune disease. By targeting the cause of the autoimmune disease rather than treating the symptoms, this type of immunotherapy offers the potential for long-lasting treatment by boosting the body’s immune system to help it fight disease.

Translation

The immune tolerance discovery was originally developed as a cell-based therapy which required the patient’s dendritic cells to be harvested then treated before being returned to the patient by intravenous transfusion.

Based on feedback from pharmaceutical companies, the original therapy was re-formatted into an injectable drug formulation by Professor Thomas, Dr Brendan O’Sullivan and Dr Nigel Davies.

The injectable format of the ASITI technology has since been the focus of translation and commercialisation.

UniQuest assisted the researchers to secure two competitive commercial grant applications and established Dendright Pty Ltd as a wholly owned subsidiary in 2005 to commercialise the ASITI technology for the treatment of rheumatoid arthritis and receive funds from the Queensland Government’s Innovation Start-up Scheme and the Australian Government’s Biotechnology Innovation Fund.

The injectable version of the ASITI technology was filed as a separate patent application and has since progressed to grant in US, Canada, China and Australia with prosecution continuing in other jurisdictions.

Autoimmune disease occurs when the body mistakes one of its own proteins (self-antigens) as foreign, resulting in an immune response.

The ASITI technology “re-educates” the body’s own immune system so that it does not react with rheumatoid arthritis specific self-antigens and offers a potentially long-lasting treatment to people who suffer from the autoimmune disease.

The leap to commercialisation required a pharmaceutical partner who recognised the potential of the ASITI technology, at a time when monoclonal antibody therapies had captured the attention of the rheumatoid arthritis market.

Most pharmaceutical companies were cautious to commit funds to antigen-specific immune tolerising induction therapy, which they considered to still be at an early stage of development.

A Successful Partnership

In 2011, a partner was identified. UniQuest pitched the technology to a senior director of new ventures from Johnson & Johnson Innovation scouting for disruptive new therapies for rheumatoid arthritis.

Around the same time, Professor Thomas had been actively communicating the scientific discovery at conferences.

The Worldwide Chairman of Janssen Pharmaceutical Companies of Johnson & Johnson, Dr Paul Stoffells, accepted an invitation to a presentation by Dendright while visiting UniQuest in Australia. He recognised the technology’s disruptive potential and UniQuest stepped up deal discussions with Janssen locally and globally.

In 2012, UniQuest facilitated a strategic research collaboration agreement between Dendright and Janssen-Cilag Pty Ltd in Australia to develop the promising rheumatoid arthritis treatment.

In 2013, Dendright signed a research and development collaboration and option-to-licence agreement with US-based Janssen Biotech, Inc. for the exclusive worldwide right to develop and commercialise the ASITI technology to treat rheumatoid arthritis.

Under that agreement, Janssen funded the remaining preclinical development through to the end of the first-in-human study.

The option-to-licence agreement included an option payment as well as development and sales milestone payments and tiered royalties.

In 2017, UniQuest brokered an arrangement with not-for-profit Arthritis Queensland as a strategic partner to contribute additional funding to the clinical program.

Clinical trials and commercialisation

The first-in-human clinical trial was conducted in Australia from 2017 to 2019.

The drug candidate was found to be generally well tolerated, which was the primary objective of the trial.

Based on other readouts from the 17 rheumatoid arthritis patient study, there was evidence of an antigen-specific response and the pharmacodynamic effect with one of the doses suggested a trend toward immunological tolerance.

Pharmaceutical companies can change their therapeutic strategy which has a knock-on effect for existing programs and their partners, regardless of the outcomes and prospects of the program.

This was the case for our program. Dendright received notice from Janssen in 2019 that the ASITI approach was no longer aligned with Janssen’s overall strategic plan for the disease area.

As a consequence, the Janssen collaboration came to an end and we are now seeking a new partner.

Janssen were clear that the ending of the collaboration was in no way reflective of the quality of the research or level of engagement in the project.

All of the intellectual property generated by Dendright and the Dendright-Janssen collaboration was subsequently returned to UniQuest and now resides with UniQuest.

The application of the ASITI technology as a treatment for rheumatoid arthritis and other autoimmune diseases is available for partnering from UniQuest.

For example, Professor Thomas’ lab at UQ has been developing a treatment for type 1 diabetes (T1D). The research received a US$1.2 million grant in 2017 from JDRF Australia and The Leona M. and Harry B. Helmsley Charitable Trust in America, to translate the ASITI technology into a treatment for T1D and advance that drug candidate through to Phase 1b clinical trials.

More recently, UniQuest has announced a partnership with CSL to develop and commercialise the ASITI technology for the treatment of Sjogren’s Syndrome.

It, along with other ASITI translation programs – and new intellectual property – are available for partnering from UniQuest.