Keynote address

Dr. Yuman Fong is a surgical oncologist at the City of Hope Medical Centre and was Keynote Speaker at this year's Bioshares Biotech Summit. As a clinician and scientist, while Dr. Fong's "day job" is surgery, he also works as an immuno-oncology researcher with his work partnered with Imugene (IMU: $0.089). Dr. Fong also has industry facing experience, having held regulatory roles in the approval process for immunotherapies and experience working with Genentech.

Dr. Fong championed collaboration as a vital process in developing new medicines. "There is the innovation and scientific rigor of academic institutions and then there's the speed and regulatory rigor of industry… when we combine the two that's when products become medicines, and when medicines make a difference in human healthcare."

This collaboration between industry and academia has been central to Dr. Fong's career and his work as a scientist. City of Hope's history of partnership was what attracted him to make the switch from New York's Memorial Sloan Kettering, stating that "they totally understood that I needed to patent all the things I make and have dialogue with industry to make it real."

Dr. Fong's latest project is oncolytic viruses, working to "find or design a virus to kill cancer". From 1990 to 2015, what Dr. Fong called the "first generation" of oncolytic viruses, only one candidate was successful in receiving approval in one indication, that being Amgen's IMLYGIC for skin cancer.

Reflecting on this minimal success, Dr. Fong stated that "the reason only one came through, even though many were in trials, was that we designed the viruses in the last generation to be much too weak to do very much." With scientists "too worried about toxicity", no trial ever went to maximum tolerated dose. "With regulators cautious, the trial path was very slow."

Mindful of this, Dr. Fong's subsequent approach was unique and elegant. His team began with the vaccinia virus, which is stable, scalable, can be administered through many different routes, and does not integrate into the human genome. Trying to "cure as many types of cancer of possible", the team chose to "let nature do it" rather than genetically engineer the virus.

Dr. Fong and his team put nine different strains of the virus into one cell, allowing lateral gene flow to take place between the strands. These new viruses were then isolated and tested against the NCI60 and 30 other cell lines to determine their cancer killing capabilities. Of the approximately seven candidates that successfully wiped out all the cancer cells, the safest compound was chosen as the lead candidate.

The team settled on CF33, which "killed everything" and is "enormously safe". The virus is "completely unique", and now completely patent protected. Dr. Fong's team was about to commence a study in triple-negative breast cancer when he was approached by Leslie Chong and Paul Hopper, CEO & MD and Executive Chairman of Imugene respectively.

Noting his distrust of "giant pharma" and recalling his work that had been "shelfed and lost all IP after it went into a committee and never came out", Dr. Fong said that a small biotech from Australia just felt right.

In May Imugene received US FDA Investigational New Drug (IND) clearance to initiate a Phase I clinical study of its oncolytic virotherapy for the treatment of solid tumours, onCARlytics, which is centred on Dr. Fong's CF33. In this platform, the CF33 virus is designed to encode a truncated human CD-19 transgene into tumour cells. The tumour cells, which now express CD19 markers, can then be targeted by CD19-CAR T therapy or anti-CD19 specific antibodies.

CD19 is a marker specific to liquid tumours such as lymphoma, and is not endogenously produced by solid tumours, which comprise 90% of all tumour types. CAR T cell therapies that have been used to treat blood cancers very effectively, often by targeting CD19, have been more limited in the treatment of solid tumours.

By adding the CD19 marker to solid tumours, Imugene is looking to enable CAR T cell and antibody therapies to combat solid tumours with a higher degree of efficacy by making solid tumours more homogenous and incorporating a clear target for immunotherapies.

Dr. Fong hailed CD19 as an exceptional target for such therapies, explaining that even if all cells producing CD19 in the body are destroyed, the patient can live an excellent life; the only downside being that they can't be vaccinated. This is contrary to targets like HER2, which is expressed in the heart and can cause complications.

The onCARlytics platform, in collaboration with Euraka Therapeutic's ARTEMIS T cells, has already generated positive preclinical data demonstrating enhanced anti-tumour activity in vivo against liver cancer. The CF33 virus has been shown clinically to have an acceptable safety and tolerability profile; no dose limiting toxicities have been documented to date in ongoing clinical trials.

Also in Phase I trials is Imugene's other oncolytic virotherapy candidate, CHECKvacc. CHECKvacc is used for the imaging, tracking, and treatment of cancer, currently being studied in triple-negative breast cancer. It has proven safe and well tolerated at dose levels 1 - 3, with City of Hope announcing in early July that the trial will proceed to the fourth dose cohort. Imugene has also reported very positive data from the Phase II study of its cancer vaccine Her-Vaxx, which showed an overall survival benefit of 5.7 months over the control.

Positive data in early stages of development is of particular importance to Imugene, with the company stating that its intention is to license or sell technologies once they generate positive Phase II data rather than become a Phase III development company.

While it is still early days, Dr. Fong is optimistic about the future of oncolytic virotherapy and other immunotherapies. Citing anti-TNF therapies that were being developed in the 1980s that are now producing yearly sales in excess of US$45B, Dr. Fong left the audience hopeful: "We were doing the work back in the 1980s, and now it's come to fruition in 2023, so you need to have a long look at it. Science still wins. If the science is good it will eventually become a medicine, a good product, and make a difference in human healthcare."

It is Dr. Fong's vision that City of Hope's collaboration with Imugene will result in CF33 being an "enabler for universal CAR T therapy".

Bioshares recommendation (Imugene):

Positive data in early stages of development is of particular importance to Imugene, with the company stating that its intention is to license or sell technologies once they generate positive Phase II data rather than become a Phase III development company.

While it is still early days, Dr. Fong is optimistic about the future of oncolytic virotherapy and other immunotherapies. Citing anti-TNF therapies that were being developed in the 1980s that are now producing yearly sales in excess of US$45B, Dr. Fong left the audience hopeful: "We were doing the work back in the 1980s, and now it's come to fruition in 2023, so you need to have a long look at it. Science still wins. If the science is good it will eventually become a medicine, a good product, and make a difference in human healthcare."

It is Dr. Fong's vision that City of Hope's collaboration with Imugene will result in CF33 being an "enabler for universal CAR T therapy".

Bioshares recommendation (Imugene): Speculative Buy Class A