Cancer immunotherapy’s use can be limited by its side effects throughout the body. Xilio Therapeutics is developing technology that selectively activates a therapy’s potent cancer-killing activity specifically at the tumor and it has raised $100.5 million to advance two programs to clinical testing.
The financing was led by Takeda Ventures. Along with the new cash, Xilio announced its new name. Until Monday, the Waltham, MA-based company was known as Akrevia Therapeutics.
Xilio’s lead programs use the validated immuno-oncology therapies anti-CTLA4 and interleukin-2. While these therapies are effective at treating cancers, they can also spark toxic effects throughout the body. Those side effects limit the number of patients that can be treated and prevent the patients who can from completing full courses of treatment, Xilio says. When the company initially launched in 2018, Tim Clackson, president and executive vice president of R&D, told Xconomy that the company’s approach involves engineering proteins with “on/off” switches. These drugs circulate in the body in the “off” state. Upon encountering cancer cells, biochemical changes switch the therapy “on” to destroy tumors.
Lead Xilio program XTX101 is an antibody that blocks CTLA-4, a receptor that acts like a brake on immune responses. It’s the same target as ipilimumab (Yervoy), a Bristol-Myers Squibb (NYSE: BMY) drug that became the first so-called checkpoint inhibitor to become approved by the FDA. That therapy is approved for treating colorectal cancer, melanoma, and renal cell carcinoma. The ipilimumab label carries a warning that the drug can cause side effects throughout the body; the most common problems affect the intestines, liver, nerves, and glands.
Xilio is also developing drugs that are engineered cytokines, a type of immune-stimulating protein. The company’s second most advanced program, XTX201, is a version of interleukin-2 (IL-2). This cytokine is approved for treating skin and kidney cancers, but side effects—such as flu-like symptoms, nausea, low-blood pressure, and diarrhea—have limited its use. Xilio says its version of IL-2 is engineered to selectively activate key immune cells inside of a tumor, an approach intended to be more effective at killing tumors while also reducing the immunotherapy’s side effects.
Xilio has not yet specificied which cancers it aims to treat but in an email, CEO Rene Russo wrote that the targets for its lead programs have been well validated in a variety of solid tumors, and the company’s goal is to study a “wide range of solid tumor types early on in the program.” Unlike some cancer therapies, treatment with Xilio drugs would not be determined by tumor type or patient-specific criteria.
“The broad applicability of Xilio agents across cancer types means that all patients could benefit from these potentially curative medicines,” Russo wrote.
Xilio’s IL-2 research puts it in competition with similar efforts by South San Francisco-based Nektar Therapeutics (NASDAQ: NKTR) which is testing its IL-2 drug bempegaldesleukin in combination with Bristol checkpoint inhibitor nivolumab (Opdivo) in a partnership that encompasses melanoma, renal cell carcinoma, non-small cell lung cancer, and bladder cancer. A separate partnership is testing the Nektar IL-2 drug with Pfizer (NYSE: PFE) drugs in prostate cancer and squamous cell carcinoma of the head and neck.
Meanwhile, Sanofi (NYSE: SNY) is betting on an engineered IL-2 drug developed by Synthorx of San Diego. The biotech, which Sanofi recently acquired for $2.5 billion, has technology that makes the protein more precise and extends its half life. Sanofi plans to test Synthorx drug THOR-707 in combination with cemiplimab (Libtayo), an antibody drug approved for treating squamous cell skin cancer, and isatuximab (Sarclisa), another antibody drug that is currently under FDA review as a potential treatment for multiple myeloma.
Xilio’s technology is based on technology licensed from City of Hope, a cancer treatment and research center in Duarte, CA, and Thomas Jefferson University. In preclinical research, Xilio says both XTX101 and XTX201 have demonstrated tumor-selective activity, which shows the potential for these drugs to treat cancer without causing limiting side effects.
The latest financing, a Series B round, added new investors SV Health Investors, MRL Ventures Fund, RiverVest Venture Partners, Bay City Capital, Solasta Ventures, M Ventures, and Ipsen Ventures. Earlier investors F-Prime Capital and Atlas Venture also participated in the funding.
Xilio says it will use the new capital to bring of its lead drugs into Phase 1 testing. An application for the FDA green light to begin clinical testing of XTX101 is expected later this year, according to the company’s website. The company expects file the paperwork for clinical testing of XTX201 in 2021. The funding will also support further development of other cytokine drugs in its pipeline. Russo said Xilio’s near-term focus is to bring its two lead programs into the clinic but “we are open to partnership opportunities if that strategically benefits our programs.”