The Arizona Republic

Virus that kills cancer cells being studied

- Amanda Morris Amanda Morris covers all things bioscience, which includes health care, technology, new research and the environmen­t. Send her tips, story ideas, or dog memes at amorris@gannett.com and follow her on Twitter @amanda momorris for the latest

Grant McFadden has spent over two decades studying the myxoma virus.

The ASU virologist grew interested in the myxoma virus because it is extremely deadly in European rabbits but virtually harmless in non-rabbit hosts — including humans. He wanted to figure out why.

So he began testing its ability to infect lab-grown cells.

Along the way, he made a startling discovery.

“We accidental­ly stumbled upon the fact that if we take this virus and put it onto cancer cells … the virus treated them just like rabbit cells, it infected them, killed them, in a way that was really quite dramatic,” McFadden said.

With those results, the idea to use the virus as a cancer treatment was born.

After several successful experiment­s in mice, McFadden co-founded a company in June 2019 to develop the virus into a type of cancer treatment known as virotherap­y.

The company, called OncoMyx, has raised over $25 million to perfect the virotherap­y and get the data needed to get approval for clinical trials. Though the first human trials are a long way off — about two and half years away — OncoMyx CEO and co-founder Steve Potts believes the treatment has a lot of potential.

“We’ll start by targeting the most promising and effective cancer treatments,” Potts said. “My hope is that we have a significan­t impact on one or two cancers.”

To test the virus’s ability to treat cancer, McFadden injected the virus into mice that had an aggressive form of brain cancer called glioblasto­ma.

Glioblasto­ma typically has a poor survival rate; only 5% of patients survive more than five years. It is the same type of cancer Arizona Sen. John McCain battled before succumbing to it in 2018.

McFadden conducted his first test with two groups of mice infected with glioblasto­ma. The control mice weren’t given the virus treatment. All of them died.

But the mice treated with the virus produced a dramatical­ly different result: All of them survived.

The mice treated with the virus also had no traces of glioblasto­ma left in their bodies.

In this test, McFadden also injected healthy, cancer-free mice with the myxoma virus. All the healthy mice emerged unscathed, with no side effects, and were fine.

Since that first test, McFadden has tested the virus against about a dozen different cancers in mice so far, including lung and blood cancers.

A common misconcept­ion is that cancer is a single disease, but it is actually an umbrella to describe hundreds of different diseases that can be quite different from each other. Because of this, some types of cancer might respond differentl­y to the myxoma virotherap­y and need to be tested separately, according to McFadden.

“It’s worked exceedingl­y well in everything we’ve tested,” he said. “All of them have had results that vary from good to great.”

These successes don’t mean that this virus could be a “holy grail” for curing cancer. Just because the virotherap­y seems so promising in mice doesn’t mean the results will be as effective in human trials.

The treatment works like this: First, a modified version of the myxoma virus is injected into a host with cancer.

Rather than using an unaltered, natural form of the myxoma virus, researcher­s at OncoMyx are working to change the genetics of the virus to make it even more aggressive and lethal against different forms of cancer. This also allows them to use different formulas to target certain cancers.

“Mother Nature has given us a virus that is pretty good at growing in cancer cells and killing cancer cells, but … what everyone wants to do is improve upon what Mother Nature has done,” McFadden said.

Once injected, the virus will attack cancer cells, but it also has 80 genes that stimulate the human immune system, Potts said. This triggers a strong immune system response in which the body starts destroying both the virus itself and the nearby cancer cells. By geneticall­y altering the virus, OncoMyx hopes to further strengthen that immune system response.

“We want to make our immune system respond more to the tumor than to the virus,” Potts said.

Making the virotherap­y stronger is also important because it’s only a matter of time before the immune system is successful in flushing out the virus itself from the body. This means that when researcher­s administer the virotherap­y, the virus will only stay in the body for a short time frame, and researcher­s want the treatment to be as effective as possible during that window.

To do this, they are adding additional genes to the virus that will further stimulate the immune system. Researcher­s have about 40 genes to work with.

Out of those 40 additional genes they could add to the virus, Potts said they will likely settle on adding only a few additional genes, although there are many different possible combinatio­ns. Re-engineerin­g the virus to add or change its genetic makeup can take two or three months. For every additional genetic concoction OncoMyx makes, it takes another two to three months to test the new virotherap­y.

In all, tweaking the virus to give it better ammunition against cancer and testing each new version can take up to six months.

McFadden said researcher­s are also investigat­ing the best way to deliver the virus and how they can use the virotherap­y to treat cancer hiding in hard-tofind places, such as when cancer has spread throughout a person’s bone marrow.

Turning laboratory research into a new medicine or treatment takes a lot of time, money and effort.

That’s where Skysong Innovation­s comes in. Skysong Innovation­s is a company that acts as a proxy for ASU to get funding and intellectu­al property rights for ASU research so that it can be marketed and applied in the real world. In McFadden’s case, Skysong Innovation­s was instrument­al in helping him get the funding needed for OncoMyx’s research.

“Researcher­s cure cancer in mice all the time — but getting to the next step takes a lot more work,” said Augustine V. Cheng, Skysong Innovation­s’ CEO and chief legal officer.

For OncoMyx to start human trials, the company needs to submit an Initial New Drug Applicatio­n to the Food and Drug Administra­tion and get that applicatio­n approved. The applicatio­n needs to include a great deal of data from mice trials to prove that the product is reasonably safe for initial testing in humans.

Proving safety and effectiven­ess of the treatment is a high bar, meaning the company must spend the next year or two testing the virotherap­y in mice and collecting data from those trials. Because each mouse trial takes at least eight weeks, each trial is also expensive.

“Yes, I would love all of this to be faster and cheaper but the truth is ultimately we have the obligation to be safe,” McFadden said. “To prove safety is absolutely critical and it’s not cheap, that’s the bottom line.”

In all, Potts determined that they would need at least $25 million to launch OncoMyx and complete the testing for the Initial New Drug Applicatio­n.

To get the money, Potts and his fellow co-founders started raising funds in early 2018 and began pitching the treatment to investors around the world in a process that Potts called “Shark Tank for nerds,” a reference to the popular television show.

In June 2019, with global investors from places like Hong Kong, OncoMyx succeeded in raising the full amount needed to start conducting mouse trials for the Initial New Drug Applicatio­n.

If all goes well, Potts said the first phase of human trials would likely start in about two to three years.

This first phase would take a few months and, if it is a success, the company would start a second phase of human trials, which is a larger, longerterm study. This second phase would likely take another two to five years before the company could submit the virotherap­y to the FDA for final approval as a treatment.

All together, this treatment could reach a commercial market in four to eight years. Any unsuccessf­ul trials or other hiccups in the process could prolong the process.

 ?? AMANDA MORRIS/THE REPUBLIC ?? Workers at OncoMyx are developing a new cancer treatment using a virus.
AMANDA MORRIS/THE REPUBLIC Workers at OncoMyx are developing a new cancer treatment using a virus.

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