Kinemed

Source: Healthcare Digital

Date :31/10/2007 06:33:21

Pathway to Success

KineMed employs both pathway-based drug discovery and translational medicine-enabled drug development. President and CEO David Fineman discusses its ground-breaking technology

Written by Abigail Saltmarsh and Produced by Thomas Venturo

US company KineMed was founded in 2001 to provide solutions to fundamental problems in disease management and drug development. Since then it has been breaking new ground and making new discoveries in medical science, by pioneering the use of in vivo molecular kinetics to guide drug discovery and development.

President and CEO David Fineman explains that KineMed’s overwhelming success over the past decade is based on its unique “pathway-based” technology.

“This is based on our ability to identify drugs with true therapeutic effect – more specifically, biochemical effects that have intrinsic functional significance and therefore predict clinical response. This is achieved by measuring the kinetics of key metabolic pathways,” he says. “By screening compounds against these dynamic targets-- – ones that are the etiological basis for important diseases - KineMed can rapidly demonstrate a drug’s on-mechanism activity in both animals and patients, as well unexpected or off-target effects.”

David Fineman cofounded the company, located in Emeryville, California, along with Marc Hellerstein, MD PHD who now chairs the scientific advisory board.

“Marc is the intellectual father of this technology,” explains David. “He is also a professor at the University of California, Berkeley, where he occupies an endowed chair. Marc has spent the last 20 years inventing and developing the underlying technology that establishes our drug development programs and that we licence exclusively from the University of California.”

A unique technology

KineMed’s business strategy is to actively pursue strategic relationships for both clinical drug development and drug discovery collaborations, while also looking for optimal in-licensing opportunities in its core areas (metabolism, atherosclerosis, diabetes and inflammation/fibrosis). Its annual revenues are in the region of $9 million - $10 million, gained largely through its collaborations with pharmaceutical companies in helping them develop pipeline compounds.

Currently the company is working on core development programs focusing on atherosclerosis, diabetes, fibrosis and osteoarthritis. Discoveries in neurogenesis and neurodegeneration fill out the portfolio.

The underlying philosophy of KineMed’s unique approach is that direct monitoring of the response to drug treatment of complex, interconnected, biological and physiologic systems (involving the output of all associated genes and proteins) allows guided, or rational, drug development. The response of integrated molecular pathways embedded in a complex biochemical network – the cell and organism- to manipulation of an isolated target is extremely difficult to predict. KineMed’s approach is to measure the drug’s ability to modulate the complex central pathways that drive the etiology of each particular disease. In this manner, targeted effects can be rapidly confirmed or refuted; unexpected therapeutic actions can be identified, patented and developed; and off-target adverse actions can also be detected early on.

“A typical biomarker measurement involves giving animals or patients a small amount of heavy water or other stable isotope-labeled tracer,” explains David. “The heavy water or other label mixes evenly and rapidly into body pool. All biomolecules made while the tracer is present are labeled as new. The cell or biomolecule of interest is then isolated from blood, tissue, saliva or urine.

Proprietary measurements of previously immeasurable pathways are achieved, utilizing ultra-sensitive mass spectrometric instruments.

The rates of synthesis, breakdown or flow in a pathway of interest are then determined, using our proprietary methods.”

KineMed’s focus is on translational medicine, the science of developing more predictive transitions from pre-clinical animal efficacy to human efficacy. Because its technology allows it to rapidly demonstrate whether a compound can effectively modulate the same metabolic pathway in both animals and man, KineMed is ideally positioned to de-risk the clinical development of new drug therapies.

“By following the biological pathways with our technology, we are able to determine the exact points at which to treat a disease,” says David. “We use authentic biomarkers - and what is unique is that we can look at the rates of change of the molecules that flow through critical pathways in the body, by use of these biomarkers.”

Collaboration

KineMed’s technologies measure the true effects of drugs, thereby providing unique insights for drug development, which are not available to other companies. To date, the company has issued nine patents (and has more than 100 pending) on its core technologies, and has validated numerous markers in animals and humans.

The company works both with pharmaceutical companies and on its own developmental projects to speed new drugs to clinical use. It currently has multiple development programs with a number of major pharmaceutical companies, including Bayer, Merck KGaA, Organon and Roche. It has also just announced a collaboration with Merck in athereosclerosis.

The non-exclusive program with Merck will see KineMed collaborate in the development of up to 10 Merck compounds for the treatment of atherosclerosis. KineMed will identify therapeutic utility in vivo preclinical and clinical models by applying its proprietary translational medicine technologies to measure cholesterol efflux. KineMed will receive $5.5million in upfront payments and up to $70million per 10 compound, based on development-success criterion.

“In this collaboration with Merck, KineMed will be using its technology to identify therapeutic activities of pipeline compounds. The collaboration preserves KineMed’s freedom to operate on its own development programs as well as partner with other companies in key disease indications,” says David.

Changing Lives

One example of this is KineMed’s pioneering work in the area of amyotrophic lateral sclerosis, also known as ALS, Motor Neurone Disease or Lou Gehrig’s Disease. This is a terminal neurodegenerative condition which currently becomes progressively debilitating, as there is no effective therapy. ALS results in profound weakness, paralysis and wasting away of the muscles, while the parts of the brain dealing with intelligence and awareness remain unaffected.

“We are working on a very accurate and so-far highly-predictive marker of the neurodegenerative process. We have been able to determine the point at which changes in this marker progress to degeneration of the nerves and muscle,” says David. “While this is not yet a cure, the results in animal models of ALS have demonstrated greater effects of delaying symptoms and extending survival than had ever been demonstrated previously. KineMed has a lead compound that is advancing into clinic in ALS that could provide significant palliative effects and improvement in the quality of life. We expect to be able to take this candidate into clinic next year.”

He adds: “What is interesting is that we are seeing the same disruption in this kinetic biomarker in other neurodegenerative conditions, including Parkinson’s disease ALS, but in a different anatomic location in the nervous system. This breakthrough may well therefore also end up being significant in the treatment of these other serious diseases as well.”