March 26, 2018

After Nasdaq woes, RXi pivots to promising cancer treatment field

Edd Cote
Melissa Maxwell works in a laboratory at RXi Pharmaceuticals in Marlborough. The company is hoping to commercialize its RNAi technology for the cancer treatment field.

In 1998, Craig C. Mello, a biologist at University of Massachusetts Medical School, and his colleague, Andrew Z. Fire, discovered a natural process known as RNA interference (or RNAi) that can be harnessed to make tiny, targeted changes in the way our genes transform our bodies. After winning the Nobel Prize for the discovery in 2006, Mello went on to cofound RXi Pharmaceuticals, where he now serves as chair of the Scientific Advisory Board.

In the two decades since the discovery, RXi has explored a variety of applications for RNAi, which can selectively prevent certain genetic information from being expressed in the body. Now, it's bringing the results of Mello's work into a burgeoning field of cancer research.

"We can, in essence, reprogram very elegantly a patient's own cells, or we can program engineered cells so that they are better armed—weaponized if you want—to attack cancer tissues more than the base-level immune system," said Gerrit Dispersyn, chief development officer at RXi.

A miracle treatment?

This type of process is part of immuno-oncology, a family of treatments that has brought new hope to people facing many types of cancer in recent years. In January, RXi announced that it was shifting its energy toward its work in oncology, and away from treatments for skin and eye diseases, where it had previously focused much of its energy.

The idea of using the immune system to treat cancers goes back more than a century, but it's made some huge leaps over the past decade. John Hallinan, chief business officer at the Massachusetts Biotechnology Council, said some immune system-based treatments have amazed doctors working in cancer treatment.

"The recovery is astounding, and some [patients] are relatively cancer-free after a regimen," he said. "It doesn't work for everybody, but it's very promising. Certain types of cancer where there's nothing else, it has proved to be nothing less than a godsend and a miracle."

Within the Massachusetts life sciences world, Hallinan said, immuno-oncology is now one of the top four most frequently researched areas.

Breakthroughs in the field didn't come out of nowhere, Hallinan said. As with many scientific advances, it depended on decades of painstaking research. But the payoff became clear over the past few years.

Immuno-oncology brings promise

For RXi, Dispersyn said, a clear signal about the practical viability of immuno-oncology research came last fall, when the FDA approved two other companies' cancer therapies using genetically engineered immune cells collected from patients. Given the promise of such methods, he said, regulators have begun greatly streamlining the process of getting them to market. Where a therapy might once have required studies on thousands of patients before it could move into clinical use, some can now reach the finish line with studies of less than 100 patients.

The federal "cancer moonshot," funded with $1.8 billion over seven years, has also accelerated immuno-oncology research, and increasing amounts of private money are going toward the work as well.

For RXi's business model, all this means that work on cancer has much greater promise in the short term than company leaders anticipated. Previously, they had anticipated that its first market-ready products would involve dermatology and ophthalmology since it already has related RNAi compounds in clinical development.

Now, though, the company—which was forced to use a reverse stock split earlier this year to boost its per-share price and regain compliance with Nasdaq Stock Market—sees oncology as its most likely path toward a viable therapy in the relatively near future. Dispersyn said it is looking for partners who can help continue the development of the dermatology and ophthalmology products.

That's not to say that the oncology applications of RXi's technology are brand new. Back in 2015, the company entered a licensing agreement with MirImmune LLC to develop cell-based cancer treatments. Then, in early 2017, it acquired the company, bringing the immunotherapy work in house.

The specific technology RXi brings to the table is a kind of RNAi compound that can deliver itself into a cell. Some other molecules that can be used to reprogram cells can't enter patients' cells by themselves because of their size or chemistry, so additional techniques, like lipid-based delivery vehicles or electric shocks, are needed to help administer the molecules. That, in turn, can make the process less efficient, or do damage to the cells, Dispersyn said.

Dispersyn said RXi's molecules are different. "We don't need any delivery mechanism or other delivery technique," he said. "These molecules get absorbed, get taken up by the cells without any other means."

That means they get into the cells with near 100-percent efficiency, and with no negative effects on the cells.

The process is relevant to a range of processes to treat diseases in which the body makes too much of a particular protein, or creates the wrong protein for a particular purpose.

Denmark testing underway

RXi is now working with several academic centers on practical applications for its technology in oncology. Inge Marie Svane of the Centre for Cancer Immunotherapy at Copenhagen University Hospital in Denmark said her organization is now testing the potential for RXi's technology in its work fighting melanoma and other cancers. Where some existing therapies inhibit proteins that cells have already produced, she said she hopes to be able to stop their production in the first place.

"It's a very new thing," she said.

"It's at a prior level, and maybe it will be more effective."

Svane said her center is beginning the testing on melanoma and will then move on to ovarian cancers and sarcoma—a type of cancer that affects connective tissues.

"I think this is a very promising principle, particularly that you can go down on the cellular level," she said.

Looking toward the future, Dispersyn said he hopes RXi will be able to get its first immuno-oncology compound into the clinical development phase in 12 to 18 months. At first, any uses of the technology will be in cases where more conventional cancer treatments have failed—something that's standard for any new therapy. Ultimately, though, the company hopes it will lead to more efficient first-line treatments that avoid the need for debilitating chemotherapy or radiation.

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