Medical Device Daily

DNA-based vaccines and immunotherapeutics company PowderMed (Oxford, UK) is aiming its “gene gun“ at a sinister and shape-shifting target: the annual influenza virus.

The company's vaccine development program is based on its Particle Mediated Epidermal Delivery (PMED) technology, a needle-free injection device that “shoots“ DNA-coated microscopic gold particles into the immune network of the epidermis.

“The device is based on ballistics, so it uses pressurized helium to actually accelerate particles into the skin,“ PowderMed CEO Dr. Clive Dix told Medical Device Daily. “By the time [the gold particles] reach the skin, they're traveling at 1,500 miles an hour.“

The particles penetrate the epidermal layer of the skin that holds the dendritic cells, which he describes as the body guards of the skin, which then activate T and B cells to initiate immune response. The targeting of this immune cell-rich tissue means that immune responses are seen with very small doses of DNA 1 to 5 micrograms a 1,000-fold less than with traditional intramuscular DNA injection.

“What the device has done for us is allow us to put the right sort of antigens in the right format into the right place,“ Dix said. “And because they are in the right place, we can use very small quantities. Because we are using small quantities, we can vaccinate more people.“

And because the PMED gene gun requires minimal medical training, allows self-administration and requires no refrigeration for stockpiling, the company said it could be particularly useful in vaccinating against emerging variants of annual flu even the avian flu, for which the company is also developing a vaccine.

“We are very excited about our lead program with the flu, not just because it will be a new and exciting product that will be beneficial to patients on an annual basis, but because we already know that we can produce enough DNA now . . . for the current avian flu to vaccinate everybody in the world,“ Dix said. “If we just make 1 kilogram, which is within the realm of the current scale of [GMP-based DNA manufacturing] facilities already commercially available, 1 kilogram will vaccinate 500 million people.“

In the event of a global health emergency, even non-healthcare workers could be trained to use the device in about 10 minutes. “That's the real vision of it; it is that simple,“ he said of the needle-free gene gun.

As described by Dix, the single-use device is comprised of a small microcylinder of pressurized helium gas; a “well-designed nozzle just like the barrel of a gun that shoots the proper ballistics“; and a small cassette with a polycarbonate membrane on each side that holds the dry formulated powder of gold and DNA.

“The way the device works is, once you have activated the safety catch which involves pressing it down onto the skin, you compress the button which breaks open the microcylinder and releases the gas into the top chamber,“ he said. “That then builds the pressure up, which is strong enough then to burst the membrane on both sides of the cassette. Then the gas rushes down the second chamber which is the barrel, and while it is rushing down it [directs] the gold particles into that stream“ and into the skin.

Dix listed several advantages of the PMED delivery method over direct injection. “We know from preclinical and the early clinical studies that we get a more robust immune response that is the most important advantage. Also, DNA in itself is a very stable structure, and the vaccine is a dry powder, so it does not need to be stored and refrigerated and it can be shipped at room temperature,“ he said. “All of these things make it a very user-friendly product as well as a very efficacious product.“

Results from a recent Phase I trial show that PowderMed's H3/Panama DNA-based influenza vaccine demonstrated cross-protective immunity against both a homologous H3 flu strain as well as four drifted heterologous H3 strains. This year, the company plans to initiate Phase II studies using both avian flu strains and annual flu strains.

“We are very confident that we have a product with the flu [application],“ Dix said. “It is just a matter of doing the development to finalize dosing schedules and the dose that we use.“

The company also has a proprietary therapeutic vaccine for the treatment of genital herpes in Phase I trials and two partnered Phase I programs in lung cancer and HIV/ AIDs. The PMED technology also is being used in Powder-Med's preclinical programs targeting genital warts and hepatitis B.

“All of the products that we're developing are either prophylactic or therapeutic vaccines,“ Dix said.

PowderMed does not currently plan to market its own products, and is pursuing in-licensing and out-licensing partnerships. The company has licensed its PMED technology to biopharmaceutical company Corgentech (South San Francisco, California) to deliver a powder formulation of a local anesthetic into the skin.

PowderMed holds the intellectual property surrounding PMED until 2025, acquired from Chiron's (Emeryville, California) 2003 buyout of PowderJect Pharmaceuticals (also Oxford). Dix, formerly director of R&D at PowderJect, co-founded PowderMed in May 2004 through a spin-out of the PowderJect PMED technology from Chiron.

Privately owned PowderMed has so far raised £ 20 million in a Series A round. Dix said that the company will move this year to do a second round of financing to take it through at least two to two and one-half years of funding, during which time the firm would be ready to go public.

No Comments