# Imugene

Imugene Ltd is a clinical stage immuno-oncology company developing a range of new and novel immunotherapies that seek to activate the immune system of cancer patients to treat and eradicate tumours. Imugene's unique platform technologies seeks to harness the body's immune system against tumours, potentially achieving a similar or greater effect than synthetically manufactured monoclonal antibody and other immunotherapies.
The company's product pipeline includes multiple immunotherapy B-cell vaccine candidates and an oncolytic virotherapy (CF33) aimed at treating a variety of cancers in combination with standard of care drugs and emerging immunotherapies such as CAR T's for solid tumours.
Imugene is a publicly traded company, listed on the Australian Securities Exchange (ASX) under the code IMU. In December 2021 it entered the S&P/ASX 200 Index, in effect making it one of the 200 largest companies on the ASX.

## History

Imugene began as a research project in the laboratory of Professor Ursula Wiedermann at the Medical University of Vienna. Over the nine years from 2004 Wiedermann et al. had developed a B cell peptide cancer immunotherapy that could induce an antibody response targeting HER-2 overexpressing tumours. In 2012 a start-up company called Biolife Science was incorporated to develop this immunotherapy (HER-Vaxx). Early-stage funding was secured from Australian and US investors in 2013, after which Biolife was taken public in December 2013 in a reverse takeover of Australian drug development company Imugene, whose name was retained after the merger.
CEO & Managing Director Leslie Chong joined the company, initially as COO, in 2015 after working at Genentech in California, USA. HER-Vaxx entered the clinic in 2017, with the company's PD1-Vaxx technology licensed from Ohio State University and the Mayo Clinic the following year. In 2019 the company then licensed the CF33 oncolytic virus platform, invented by renowned oncologist Professor Yuman Fong of City of Hope Cancer Center in California, USA. In 2021 it also licensed the onCARlytics technology developed by Professor Fong. The company's CHECKvacc (2021) and VAXINIA (2022) technologies have also subsequently entered the clinic.

## Oncolytic virus technology

onCARlytics (CF33-CD19) is a novel immunotherapy utilising the CF33 oncolytic virus to deliver and present CD19 antigen on the surface of cancer cells promoting utilisation of combination with CD19 targeting agents against solid tumours. Researchers first created an oncolytic virus (CF33-CD19) in the lab of City of Hope's Professor Yuman Fong, M.D., to get into tumour cells and start producing CD19. They did this successfully in triple-negative breast, pancreatic, prostate, ovarian, head and neck, and brain cancer cell lines. CF33-CD19 oncolytic virus was then combined with CD19 CAR T cells in vitro and in vivo mice studies. Researchers showed significant activity with mice being cured of their cancer with the CF33-CD19 and CAR T-cell combination, as well as prolonged protective anti-tumour immunity. Solid tumours don't express CD19 on their cell surface, therefore introducing the CF33-CD19 allowed for CD19 to be present on the solid tumour cell surface, as well as helped to reverse the tumour's harsh microenvironment, making it receptive to receiving CAR T-cell therapy.

## B-cell immunotherapies

B-cell immunotherapies link an immunogenic protein with a B-cell epitope and incorporate an adjuvant to produce a B-cell cancer vaccine that induces the body to produce antibodies against the normal self-proteins, such as HER2 or PD-1 (known as breaking immune tolerance). The antibodies produced following the vaccination are a ‘polyclonal’ mixture of antibodies that bind to different parts of the vaccine antigen.
HER-Vaxx is a B-cell immuno-therapy designed to treat tumours that over-express the HER-2/neu receptor, such as gastric, breast, ovarian, lung and pancreatic cancers. Developed by leading scientists at the Medical University of Vienna in Austria, the immuno-therapy is constructed from several B-cell epitopes derived from the extracellular domain of HER-2/neu. It has been shown in pre-clinical studies and in Phase I studies to stimulate a potent polyclonal antibody response to HER-2/neu, a well-known and validated cancer target.
PD1-Vaxx is a B-cell immuno-therapy which aims to induce the body to produce polyclonal antibodies that block PD-1 signalling, and thus produce an anticancer effect similar to Keytruda, Opdivo and the other immune checkpoint inhibitor monoclonal antibodies that are transforming treatment of a range of cancers. PD1-Vaxx has shown great potential in preclinical studies. It outperformed an industry-standard mouse anti-PD-1 antibody in a mouse model of colorectal cancer.
Developed by Professor Pravin Kaumaya at the Ohio State University in Columbus OH, the immunotherapy is constructed from a single B cell epitope derived from the extracellular domain of PD-1. .

## Main people

Imugene's Executive Chairman is Paul Hopper, an Australian bioentrepreneur based in Sydney who was instrumental in identifying the HER-Vaxx project and taking it public in Imugene. The company's CEO and Managing Director is Leslie Chong, who used to be a Senior Clinical Program Lead at Genentech in San Francisco.