BioWorld International Correspondent
Efforts by Zealand Pharma A/S to establish modulators of gap junction proteins as a new therapeutic category have received a big pharma-sized boost in the shape of Wyeth, which has entered an agreement based around a peptide, ZP123, that appears to offset ventricular arrhythmia (dangerously abnormal heart beat) by modulating gap junction activity.
Jacob Dynnes Hansen, chief financial officer of Glostrup, Denmark-based Zealand, told BioWorld International he was unaware of any other biotech-pharma collaborations focused on that area. "This is a compound deal based on ZP123. It just happens to be the first agreement based on gap junction modulation," he said.
Terms of the agreement were not disclosed. The companies will cooperate on further preclinical development of ZP123. "We expect that will move into clinical development within a short period," Hansen said. Madison, N.J.-based Wyeth would then take on the clinical development program. Zealand will receive research fees, plus milestone payments and royalties on eventual product sales. Hansen said that over its life the deal will make "a considerable contribution" toward funding the company's operations.
Although defined as a two-year pact initially, it includes provisions for two one-year extensions. Wyeth has also negotiated an exclusive option for a broad collaboration program to identify additional compounds that act on gap junction channels. Although the current focus of the agreement is on cardiac disease, Hansen said there is nothing in it that would prevent a move into other indications.
Gap junction channels play a central role in intercellular communication throughout the vertebrate world. They are composed of connexins, membrane-bound protein building blocks that allow free passage of ions and small hydrophilic molecules among neighboring cells, thereby contributing to overall physiological coordination of tissues and homeostasis.
Disruptions to gap junction channels are implicated in a variety of conditions. ZP123, Hansen said, appears to have a selective effect on impaired gap junction channels. "What we have been able to show is that we can re-establish gap communication in cells under stress. We see no effect on normal cells."
Biological understanding of gap junction functioning is still at an early stage of development, and Zealand does not have a screening system in place for detecting lead compounds. "What we have done so far is extrapolated from known peptides and modified in various ways their chemical structures and applied them in various ways to gap junction models," Hansen said. ZP123, he said, was modeled on the anti-arrhythmic peptide AAP10, although its precise mode of action is not understood. "It's still early in terms of getting a full insight into the mechanism," Hansen said.