Nearly two years after terminating a license agreement with Medtronic Inc. for the delivery of Resten-NG, AVI BioPharma Inc. signed a new partner that will provide up to $100 million in funding for the program, as well as two others.
The partner, Cook Group Inc., has licensed AVI’s Neugene antisense technology for down-regulating c-myc gene expression in the field of cardiovascular disease. It will assume all clinical development activities of AVI’s Resten-NG drug-eluting stent program, Resten-MP microparticle delivery program and its new project for the catheter delivery of Resten-NG.
"This is a very big deal," said AVI’s director of investor relations, Michael Hubbard. "Part of the reason we did it is in the interest of focus."
Portland, Ore.-based AVI primarily is focused on its infectious disease program in the areas of hepatitis C and influenza A, including avian influenza type H5N1. It has Phase I trials planned for AVI-6001 for avian flu, and AVI-6002 for Ebola virus, as well as for a muscular dystrophy product. The company also has completed a Phase I trial of AVI-4557 for drug metabolism, and a Phase II trial of AVI-4065 for hepatitis C. It is planning Phase II trials later this year for its coronary artery bypass graft drug, AVI-5126.
But the company’s most advanced products - the ones partnered now with Bloomington, Ind.-based Cook - are Resten-MP, an intravenous drug in Phase II trials for restenosis; and Resten-NG, which is set to enter Phase III trials also for restenosis. Both products employ devices, such as drug-eluting stents or AVI’s proprietary microparticle delivery method, which uses bare-metal stents.
"We’re not a device company. Cook is," Hubbard said. "This is perfect timing and a perfect partner."
Cook will fund all development, clinical and regulatory costs of the programs in both the U.S. and Europe - a commitment that could translate into as much as $100 million - and it has signed a supply agreement with AVI, but those terms were not disclosed. In lieu of near-term milestone payments, AVI opted for a double-digit royalty on worldwide product sales of its Neugene drugs for vascular disease, a decision based on the drugs’ established Phase II efficacy.
Terms also call for Cook to buy 692,003 shares of AVI common stock - a $5 million equity purchase. And the device company will take over AVI s facilities and personnel at its Colorado site.
"I certainly think the potential of these [programs] moving along will be higher in Cook’s hands," Hubbard told BioWorld Today, "where they have considerably more horsepower."
The agreement with Medtronic Inc., of Minneapolis, which began in May 2001, did not cover the microparticle or catheter delivery programs - only the drug-eluting stent program. It was terminated in the summer of 2004. (See BioWorld Today, May 24, 2001.)
"It didn’t move forward, and we felt that it needed to go into other hands," Hubbard said, "so we let the agreement expire and we took back the license to Resten-NG."
Resten-NG, also known as AVI-4126, is a third-generation antisense agent that targets c-myc, the key gene involved in cardiovascular restenosis. It appears to regulate downstream genes that produce the pathology of restenosis, such as cell migration and adhesion, collagen formation, secretion of extra-cellular matrix and cell proliferation.
The c-myc gene expression is activated by an injury to the vascular lining during angioplasty and stent placement. It peaks 24 to 48 hours before subsiding, but Neugene antisense drugs are able to prevent the process because they can be delivered immediately following injury through a catheter, stent elution, or through AVI’s microparticle delivery system, Resten-MP.
"The advantage of this product is it’s gene-targeted. It down-regulates a gene in a very quick fashion," Hubbard said. "It doesn’t need to be around a long time. You don’t run into toxicity issues."
An added benefit when AVI’s microparticle technology is used is price. Bare-metal stents "are about one-tenth the costs of drug-eluting stents," Hubbard said.
AVI raised $23 million in November through a direct equity placement, which was expected to provide it with two years worth of cash, although it might last longer now that the Neugene cardiovascular programs are partnered with Cook. (See BioWorld Today, Nov. 16, 2005.)
The company’s stock (NASDAQ:AVII) climbed 53 cents on Monday’s news, closing at $6.96.