A small San Diego biotech has identified a drug that appears to prevent several subtypes of the human papillomavirus (HPV) from replicating—including the two HPV subtypes that cause 70 percent of all cases of cervical cancer.
“It’s early, so we shouldn’t hype it too much. But the antiviral studies look pretty good,” said Karl Hostetler, an emeritus professor of medicine at UC San Diego, and the founding CEO of Hera Therapeutics. The two-year-old startup has been incubating in the Janssen Labs life sciences accelerator in San Diego.
Research findings being presented in Seattle this weekend during the 29th Annual International Papillomavirus Conference show that HTI-1968, a small molecule discovered in Hostetler’s lab, blocked the replication of HPV-11, HPV-16, and HPV-18 in cultured human cell models. The National Institute of Allergy and Infectious Diseases funded the studies, which were done by Louise Chow and Thomas Broker at the University of Alabama, Birmingham.
If the early results hold up, Hera Therapeutics could potentially become the first biotech to develop a direct-acting antiviral therapy for HPV. (The drug would be applied topically to the skin, Hostetler said.) But that’s a big “if”—and a number of biopharmaceutical rivals are already in clinical trials with immunotherapy products to treat HPV infections or HPV-related cancers, including Pennsylvania’s Inovio Pharmaceuticals (NYSE: INO).
Two HPV vaccines also have been commercially available for years. The FDA approved Merck’s Gardasil in 2006, and authorized additional uses three years later. The agency also approved GlaxoSmithKline’s Cervarix in 2009.
Both HPV vaccines are designed to trigger the production of antibodies that are keyed to neutralize specific types of HPV (more than 40 subtypes can infect the genital area), including HPV 16 and HPV 18, the subtypes responsible for 70 percent of all cervical cancers—and that are also associated with cancers of the vulva, vagina, penis, anus, and throat.
You might think that would end the matter, in much the same way that vaccines halted the spread of polio and eradicated smallpox. But in the U.S., only 38 percent of the eligible girls and 14 percent of eligible boys received all three recommended inoculations against HPV last year, according to a national immunization survey.
Meanwhile, HPV is the most common sexually transmitted infection in the United States, according to the Centers for Disease Control, with an estimated 6.2 million persons becoming newly infected every year. More than 80 percent of American women will contract at least one strain of HPV by age 50. In most cases, the symptoms of HPV infections go away on their own, but the virus remains, and HPV-16 and HPV-18 infections can eventually lead to cancer.
Of the estimated 12.7 million cancers occurring globally in 2008, one study estimates that about 610,000 (4.8 percent) could be attributed to HPV infection.
There is no cure for HPV infections; the vaccines are only preventative.
So HPV vaccines cannot be used to treat people after they’re infected with HPV. Hostetler said some studies even suggest that HPV vaccines lack efficacy once people become sexually active. With no antiviral therapies for HPV available, the current standard of care for HPV infections among women calls for close monitoring, frequent Pap smears, and in some cases, occasionally freezing or surgically excising abnormal tissue.
Hostetler founded Hera Therapeutics in 2012, and so far has raised $2.4 million, mostly from individual investors. He is an expert in the design, synthesis, and evaluation of antiviral drugs for poxviruses as well as for cytomegalovirus, herpes simplex, and other double stranded DNA viruses. He was previously a founder of three companies developing drugs to treat serious viral infections and cancer—San Diego-based Vical and two biotech’s in Durham, NC; Chimerix (NASDAQ: CMRX) and Triangle Pharmaceuticals, acquired by Gilead in 2003 for $464 million.
The drug under development at Hera Therapeutics works by blocking viral DNA synthesis in the three HPV subtypes. Hostetler said his lab at UCSD identified HTI-1968 and other potential antiviral compounds using a new medicinal chemistry platform.
The company plans to complete pre-clinical studies over the next year or so, and wants to develop HTI-1968 as a topical treatment for chronic infections caused by HPV-16 and HPV-18. Over time these HPV subtypes produce oncoproteins that lead to cancer. But “if you could stop this virus and eliminate it” through early intervention, Hostetler said, “then nothing could happen downstream.”