Health

HEALTH • Spring 2018 15 H Geert Cauwenbergh, president and CEO, RXi Pharmaceuticals Immuno-Oncology drugs in development Source: Cancer Research Insititute, Landscape of Immuno-Oncology Drug Development, Dec. 7, 2017 T-cell targeted immunomodulator 199 54 12 22 5 6 Other immunomodulator 284 72 24 42 24 8 Cancer vaccine 261 130 33 144 30 7 Cell therapy 179 112 12 96 2 Oncolytic virus 95 34 12 16 2 CD3-targeted biospecific mb 46 29 1 TOTALS 1,064 431 93 320 61 24 Preclinical and discovery Phase I Phase I/II Phase II Phase III Approved came last fall, when the FDA approved two other companies' cancer therapies using genetically engi- neered immune cells collected from patients. Given the promise of such methods, he said, regulators have begun greatly streamlining the process of get- ting 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 immu- no-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 treat- ments. 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 repro- gram cells can't enter patients' cells by themselves because of their size or chemistry, so additional tech- niques, 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 oncol- ogy. 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 pro- duced, 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, particu- larly 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-oncol- ogy compound into the clinical development phase in 12 to 18 months. At first, any uses of the technolo- gy 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 treat- ments that avoid the need for debilitating chemo- therapy or radiation. Gerrit Dispersyn, chief development officer, RXi Pharmaceuticals

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