Dynavax Technologies Inc., of Berkeley, Calif., has had a busy week, with a $27 million financing announced Tuesday followed by a paper in the Oct. 5, 2006, New England Journal of Medicine reporting positive results of its vaccine against ragweed allergies.
News of the NEJM article sent Dynavax's stock rocketing - it finished Thursday up $2.74, or 55.2 percent, to close at $7.70. Dynavax CEO Dino Dina told BioWorld Today that finishing the financing before the publication of the NEJM article was the "prudent approach," adding that "obviously we were aware of news flow, and we felt we needed to finish the financing before the article came out."
He also said that even though a financing at $4.40 was "not exactly glamorous," the money has given the company "a very solid financial position," which means the company can go about business. "So we''re happy with that," he said.
Dina would not comment on whether he found the sharp uptick surprising, saying that he "never has any expectations" on stock price, because predicting the market's response is "an impossible art, at least for me."
But it is worth noting that the data reported in NEJM is from the 2001 and 2002 ragweed allergy season, and the findings have since been replicated in much larger trials, meaning that what is in the NEJM data is not really new.
Not that that makes the data less impressive. In the research reported in NEJM, patients with ragweed allergy received six injections of Dynavax's Tolamba vaccine at weekly intervals before the beginning of the 2001 hay fever season.
The doctors then measured allergy symptoms, including antibody and cytokine responses, physical responses such as runny noses and sneezes, and the use of allergy medication.
Compared to those who received a placebo injection, patients who received Tolamba injections in 2001 had sharply reduced allergy symptoms during both the 2001 and 2002 allergy seasons. Tolamba blocked the seasonal rise in ragweed-specific IgE in allergic individuals, and reduced levels of the pro-inflammatory cytokine interleukin-4.
Six injections may sound like a lot, but it's a true bargain compared to standard immunotherapy, which can require 60 to 90 injections over three to five years. Unsurprisingly, compliance with such a regimen is low, and Dina said that "Very few people have the time or stamina to go through with all that."
Tolamba consists of an immunostimulatory DNA sequence that binds to Toll-like receptor 9. The immunostimulatory sequence is derived from bacteria, which use it to suppress the host immune response during an infection. By linking the sequence to a protein that is the most allergenic part of the ragweed plant, the scientists were able to tone down the immune response to ragweed by up-regulating some types of T-helper cells and down-regulating others.
A serendipitous effect of the way Tolamba is designed is that one ragweed protein molecule links, on average, to four immunostimulatory DNA molecules, and the DNA forms "a halo, or fuzz," around the allergen, Dina said.
As a result, IgE molecules are unable to bind to the allergen directly - and it is IgE crosslinking that causes massive histamine release and the most feared type of allergic reaction, anaphylactic shock, which can be fatal.
As a result, Dina said, in more than 7,000 individual injections, not only has there not been a single anaphylactic reaction, but also, "I don't believe we have had a single allergic event."
This is not lost on physicians, who are impressed by the safety.
Long-term, the company plans to expand the reach of its technology to other allergies; Dina named specifically peanut allergies, and said that Dynavax has animal data indicating that the technology can prevent anaphylaxis. "Tolamba and ragweed is only one piece of what can be done with this technology," he said.
Dina said that when the current clinical trials are completed, he expects that Dynavax can begin working with the FDA to "start putting in place a BLA scheme."
He expects that the company will need to conduct two additional trials that relate to biologics manufacturing rather than safety or efficacy data, though he cautioned that this is only an educated guess.
The results reported in NEJM have since been essentially replicated in several larger trials, and three large trials currently are ongoing.
Most recently, data from a two-year, multi-center Phase II/III Tolamba trial was presented at the annual meeting of the American Academy of Allergy, Asthma & Immunology in March 2006.
The trial replicated the results of giving one set of injections, but it also found some counterintuitive results of what happens if patients receive a set of booster shots a year later: While the boosters did not completely erase the benefits of the vaccine, patients who received booster shots did significantly worse the second year than those who did not.
"We were all blindsided by that," Dina said, adding that they believe that the second-year booster shots draws T cells away from the nose, where they can fight the environmental allergen, and to the lymph node, where the allergen is being presented via the booster shot. He noted that from the point of view of patients, the fact that one year's worth of injections is better than two is positive.
"It works - and you don't even need a booster," he said.