Imugene progresses novel cancer-killing virus with first patients dosed in combination trial

Immuno-oncology company, Imugene (ASX: IMU) has begun dosing the first patients of its combination study evaluating its novel cancer-killing virus (CF33 oncolytic virotherapy) in metastatic advanced solid tumours (MAST).

Imugene is developing a range of therapies that are designed to activate a cancer patient’s immune system to help it fight its malignant cells.

By essentially harnessing a patient’s own immune system, malignant tumours can potentially be eradicated.

The company is investigating its treatments as sole therapies (monotherapies), and in combination with other marketed drugs.

Imugene’s portfolio includes multiple immunotherapy B-cell vaccine candidates, an oncolytic virotherapy (VAXINIA or CF33), and emerging technologies, including onCARlytics (CF33 CD19) in combination with CAR-Ts ,or bispecifc antibody targeting CD19 for solid tumours.

VAXINIA MAST trial progresses

The company is progressing its novel cancer-killing virus CF33-hNIS (VAXINIA or CF33), which is delivered to patients via intravenous (IV) and intra-tumoral methods (IT).

Imugene is evaluating VAXINIA as a monotherapy and in combination with pembrolizumabin in patients with MAST.

In early March, the first patients in the IV and IT cohorts received VAXINIA in combination with pembrolizumab.

Last month, Imugene reported it was on its third cohort of three-to-six patients evaluating VAXINIA as a monotherapy at escalating doses.

All patients have had at least two prior lines of standard of care treatment.

Patients treated to-date have received the lowest doses of VAXINIA and have shown what Imugene describes as “acceptable safety”, which allowed for escalating monotherapy doses and evaluation of the virus in combination with immunotherapy pembrolizumab.

These studies kicked-off in May 2022 and are expected to take 18-24 months to complete. All-up, the company hopes to recruit up to 100 patients across 10 trial sites in the US and Australia.

CF33 oncolytic virotherapy platform

Imugene licenced the CF33 oncolytic virus platform in 2019 from Prof Yuman Fong, who is the chair of the Department of Surgery at City of Hope in the United States.

City of Hope is an independent research and treatment centre for cancer, diabetes and other life-threatening diseases based near Los Angeles.

Imugene describes Dr Fong as a world-renowned cancer researcher, physician and surgeon.

In pre-clinical laboratory research and mouse models, CF33 was able to shrink malignant colon, lung, breast, ovarian and pancreatic tumours.

The virus effectively works by finding, infecting and killing only cancer cells.

Imugene managing director and chief executive officer Leslie Chong said the company was “incredibly eager” to unlock the potential of CF33 and the oncolytic virotherapy platform for cancer patients.

CHECKvacc and onCARlytics

Also, under development within Imugene’s portfolio are its CHECKvacc and onCARlytics therapeutics.

CHECKvacc, also known as CF33-hNIS-antiPD-L1, is an armed chimeric vaccinia poxvirus, which is designed to selectively kill tumour cells while also activating the immune system.

The immunotherapy is undergoing a phase 1 trial in patients with metastatic triple negative breast cancer – targeting the PD-L1 protein and activating the local tumour microenvironment.

CHECKvacc was injected into the tumour and was found to be safe and well-tolerated in all patients in cohort two and initial results also showed immune activation in response to the therapy. The study is currently in cohort three.

onCARlytics combines CF33 and CD19 with CD19 directed therapeutics to include CAR-T (chimeric antigen receptor) therapies.

To-date CAR-T, alone, has limited activity in solid tumours. According to Imugene, this is because of a lack of selectively and highly expressed surface antigens such as the blood B cell transmembrane protein CD19 present on solid tumours.

CD19 is present in both normal and abnormal B cells. Because of this, it is expressed in most B-cell malignancies and at an early stage.

Imugene has designed onCARlytics to express CD19 on solid tumours following infection of the cancer cell by the CF33-CD19 virus – enabling them to be “seen” by targeted therapies.

PD1-Vaxx

In February, Imugene revealed it has been granted the patent for its PD1-Vaxx, which is a B-cell activating immunotherapy for treating non-small cell lung cancer.

It essentially works by preventing cancer cells from using programmed death-1 (PD-1) to stay undetected by the immune system.

PD-1 is a protein that is found on T-cells, which is a type of immune cell. Unfortunately, when PD-1 is bound to another protein PD-L1, it can prevent T-cells from killing other cells including cancer.

Imugene’s PD1-Vaxx is under clinical development and the recent patent protects the company’s intellectual property through to 2038.

Ms Chong said it is vital to the company to continue “locking-in” its IP across its portfolio.

“With the US being the largest healthcare market in the world, this is a particularly important patent to protect our PD1-Vaxx technology as we continue its development,” Ms Chong added.

Anti-cancer effect

PD1-Vaxx has been designed to treat tumours like lung cancer by interfering with the PD-1 checkpoint target and generate an anti-cancer effect.

By inhibiting the PD-1 protein, Imugene’s PD1-Vaxx boosts the ability of its T-cells in killing the cancer cells.

Imugene has completed the final preparations for a new trial evaluating PD1-Vaxx in combination with immune checkpoint inhibitor atezolizumab (Tecentriq).

HER-Vaxx

Another of Imugene’s B-cell immunotherapies is its clinically advanced HER-Vaxx, which has been designed to treat tumours that overexpress the HER-2 receptor.

These receptors are essential in controlling cell growth and differentiation. Overexpression of the HER-2 receptor is associated with adenocarcinomas, including gastric cancers.

During pre-clinical studies, HER-Vaxx was seen to stimulate a potent polyclonal antibody response to HER-2 receptors.

Clinical results from a phase 2 study involving a combination of HER-Vaxx and chemotherapy was undertaken in patients with HER-2 overexpressing metastatic or advanced gastric adenocarcinoma.

The combination of HER-Vaxx and chemotherapy increased overall survival in study participants to 14 months compared to 8.3 months with chemotherapy alone.

Further trials using HER-Vaxx in combination with other therapies have begun.