By Mary Welch
CpG ImmunoPharmaceuticals raised $12.9 million in a second-round venture financing to advance CpG 7909 and CpG 8916, its immune stimulation products, through Phase I/II trials.
The Wellesley, Mass-based company develops products to incite the immune system against cancer, infectious diseases, allergy and asthma and to help protect against opportunistic infections after cancer chemotherapies. The products are based on CpG DNA, a technology that promotes white blood cell proliferation and rapidly activates both cellular and humoral immune responses.
"It's a hefty amount of money and it'll be enough for us to see some significant clinical results," said Robert Bratzler, the company's president and CEO. "This will let us have a good idea in humans about what the compounds do in cancer, infectious diseases, allergies and asthma and see if they produce the same results as we saw in preclinical trials with animals."
TVM Techno Venture Management, of Munich, Germany, was the lead investor. Other investors included Alafi Capital Co., of San Francisco; Qiagen NV, of Hilden, Germany; Alpinvest Holding NV, of Naarden, the Netherlands; Kredietbank S.A. Luxembourgeoise, of Luxembourg; and Mulligan Beteiligungs GmbH, of Hamburg, Germany.
The company raised $6.3 million in seed financing in 1997.
The lead candidate, CpG 7909, already is in a Phase I safety trial in Canada for hepatitis B and will start Phase I in the U.S., Canada and Europe for a cancer vaccine and a cancer safety trial, as well as an allergy/asthma trial, an allergy/asthma safety trial and one for flu. The cancer safety trial is a forerunner of a non-Hodgkin's lymphoma efficacy trial, Bratzler said.
The second compound, CpG 8916, is slightly behind in development but still should be in the clinic this year for cancer, he said.
"We'll be starting these six trials as soon as possible," Bratzler said. "The INDs [investigational new drug applications] will be filed in the next couple of months as will the equivalent filings in Canada and Europe. We'll be able to see some clinical data and assess it by the fourth quarter and for all the trials by fall 2000."
CpG DNA was discovered by the company's co-founder, Arthur Krieg, while he was an associate professor at the University of Iowa College of Medicine. He determined that specific short stretches of DNA containing cytosine-guanine dinucleotides (CpG) are powerful activators of immune cell proliferation and humoral immune responses. Not only does CpG DNA provoke strong cellular immune responses but slight variations of it in CpG DNA sequences can alter immune responses, thus allowing researchers to potentially create highly specific therapies.
CpG dinucleotides are somewhat rare in human DNA but are common in the DNA of infectious organisms such as bacteria. Krieg and his colleagues found the immune system sniffs out bacteria and viruses not only by the invaders' protein coats, but also by patterns in the microbes' DNA.
"Vertebrate DNA and bacterial DNA have a subtle chemical difference," Krieg told BioWorld Today in an earlier interview. "This had been realized for many years, but apparently it hadn't occurred to anyone previously that our immune system might recognize the difference." (See BioWorld Today, Oct. 15, 1997, p. 1.)
It seems that the human immune system recognizes CpG dinucleotides as an early warning sign of infection and, when CpG DNA enters a cell, it activates genes that jump-start the immune system.
Preclinical studies seemed to support the company's platform. Ordinarily, three shots of a hepatitis B vaccine would provide 90 percent protection but, when DNA was added, all 55 monkeys developed protective antibody levels after a single dose, the company said.
"We believe that a similar result will be produced in humans and that's why we're raising the money to test it in humans," said Bratzler. "The flu trial is also interesting. We can achieve the same flu protection even after reducing the flu antigen by a 10-factor, and maybe even greater. There is a fear that the country may run out of vaccine and, using our method, that shouldn't be an issue."