KineMed Inc. granted Merck & Co. Inc. nonexclusive rights to identify and develop up to 10 compounds for atherosclerosis using its reverse cholesterol transport (RCT) technology, in exchange for more than $5.5 million in initial and research payments and up to $70 million in milestones per compound.

It's a deal that could provide "good economics for us," said David Fineman, president and CEO of Emeryville, Calif.-based KineMed, a pathway-based drug discovery and development firm that relies on its translational medicine technology both as a predictive tool and to confirm therapeutic clinical activity.

In the atherosclerosis space, in which the primary focus has turned from treating the symptoms to treating the disease, those capabilities are critical, Fineman added, particularly in the wake of safety concerns regarding Pfizer Inc.'s investigational cholesterol drug torcetrapib, which led to the shutdown of Phase III testing late last year.

Hoping to pick up the slack from waning sales of cholesterol-lowering drug Lipitor, New York-based Pfizer tried linking Lipitor's LDL-lowering ability with a compound designed to increase HDL, or "good," cholesterol by targeting cholesterol ester transfer (CTEP). But the resulting product, torcetrapib, was yanked from development in December after too many deaths were reported in Phase III studies. "That study blew up because the HDL they were raising" ended up having an "off-target effect," Fineman said, adding that "CTEP is now under question as an appropriate target for treating atherosclerosis." (See BioWorld Today, Dec. 5, 2006.)

In its deal with Whitehouse Station, N.J.-based Merck, KineMed will use its RCT technology to evaluate compounds provided by Merck. "We will test them in various stages of preclinical and clinical development," he told BioWorld Today, and will determine on-target and off-target effects and on-mechanism effects so Merck can decide which programs to advance.

An advantage to KineMed's technology, Fineman said, is its symmetry, or the ability to use the same tests in animals as in humans, which "has tremendous value in the area of translational medicine and really allows us to take [discoveries] from the bench to the bedside." Or more specifically, the RCT platform enables the company to identify compounds and then, during development, "make sure those compounds continue to do what they're developed to do."

In addition to the initial payments, research funding and milestones, the deal with Merck could include milestones for other undisclosed conditions.

The multibillion atherosclerosis market is one of KineMed's core indications. Beyond the Merck collaboration, the company is working on additional approaches.

In May, it gained an option to exclusively license rights to scavenger receptor-class B type I (SR-B1) as a therapeutic target for atherosclerotic heart disease from the Massachusetts Institute of Technology. That biomarker is "the place HDL cholesterol docks in the liver to discharge bad cholesterol," Fineman said, and might prove significant "given that the CTEP marker has been under a cloud since the Pfizer debacle."

Also in May, KineMed presented promising animal-model data on a method for measuring the efflux of cholesterol from tissues through its RCT platform, which represents the mechanism by which excess cholesterol can be removed from tissues.

Outside of atherosclerosis, KineMed has ongoing collaborations with several firms, such as Vancouver, British Columbia-based Forbes Medi-Tech Inc., Tokyo-based Sosei Co. Ltd. and Organon A/S, of Oss, the Netherlands. Earlier this year, KineMed added an agreement with Bayer HealthCare AG, of Leverkusen, Germany. Those deals involve "the other aspect of the company's business," Fineman said, which is to use its translational medicine technology to repurpose existing compounds.

The firm also is working on its own internal pipeline, leading off with KM801, a small molecule in development for amyotrophic lateral sclerosis. The compound, which showed an ability in preclinical studies to alter microtubule dynamics in nerve cells, is expected to start Phase I testing in the second half of 2008. The company recently completed a $15 million convertible note offering to push that work forward.