Concert Pharmaceuticals - Building Better Medicinse
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Technology

Introduction: Building Better Medicines

We are a clinical stage biopharmaceutical company applying its extensive knowledge of deuterium chemistry to discover and develop novel small molecule drugs. Our approach starts with approved drugs, advanced clinical candidates or previously studied compounds that we believe can be improved with deuterium substitution to provide better pharmacokinetic or metabolic properties and thereby enhance clinical safety, tolerability or efficacy. We have executed on this approach to become a clinical stage biotechnology company and are developing a robust pipeline of product candidates in several therapeutic areas.

We apply our DCE Platform to systematically identify approved drugs, advanced clinical candidates or
previously studied compounds that we believe can be improved with deuterium substitution. Potential
advantages of our selective deuteration include:

  • Improved metabolic profile. We have selectively deuterated compounds and compounds produced by
    metabolism of other compounds, which are called metabolites, to improve their metabolic profiles by
    reducing the formation of toxic or reactive metabolites or by increasing the formation of desired,
    active metabolites relative to the corresponding non-deuterated compound. The improved metabolic
    profile may potentially reduce or eliminate unwanted side effects or undesirable drug interactions.
  • Improved oral bioavailability. We have selectively deuterated compounds to reduce the extent of
    undesired metabolism in the wall of the intestines and in the liver, referred to as first-pass metabolism. This resulted in a larger percentage of unmetabolized drug reaching the target site of action. Deuterated compounds with improved bioavailability may be active at lower doses.
  • Increased half-life.We have selectively deuterated compounds to prolong their pharamacokinetic
    profile, which is an increase in the half-life of the compound in the body. This may decrease the
    number of doses that a patient is required to take per day or provide more consistent exposure of the compound in comparison to the corresponding non-deuterated compound.

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DCE Platform® - More Efficient and Less Expensive

Unlike traditional methods of drug discovery which involve lengthy processes with high failure rates, our approach generally begins with approved drugs, advanced clinical compounds or previously studied compounds.  We prioritize candidate compounds based on medical need, commercial opportunity, competitive and patent landscapes and internal strategic fit.  We believe our approach may enable drug discovery and clinical development that is more efficient and less expensive than conventional small molecule drug research and development. [back to top]

A Novel Drug Discovery Paradigm

The average adult human body contains approximately two grams of deuterium. While essentially
identical to hydrogen in size and shape, deuterium differs from hydrogen in that it contains an additional
neutron. As a result, deuterium forms a more stable chemical bond with carbon than does hydrogen. The
deuterium-carbon bond is typically six to nine times more stable than the hydrogen-carbon bond. This
has important implications for drug development because drug metabolism often involves the breaking of
hydrogen-carbon bonds.

 

Because deuterium forms more stable bonds with carbon, deuterium substitution can in some cases alter
drug metabolism, including through improved metabolic stability, reduced formation of toxic
metabolites, increased formation of desired active metabolites, or a combination of these effects. At the
same time, because deuterium closely resembles hydrogen, the substitution of deuterium for hydrogen
has generally been found not to materially alter the intrinsic biological activity of a compound.
Deuterated compounds can generally be expected to retain biochemical potency and selectivity similar to
their hydrogen analogs. The effects, if any, of deuterium substitution on metabolic properties are highly
dependent on the specific molecular positions at which deuterium is substituted for hydrogen. In
addition, the metabolic effects of deuterium substitution, if any, are unpredictable, even in compounds
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Deuterated Product Pipeline

Our DCE Platform consists of the proprietary know-how, techniques and information that we have
developed over the past seven years. Deuterated compounds can have an increased half-life in the body
and increased systemic exposure as compared to their corresponding non-deuterated analogs, which we
believe can lead to benefits such as improved safety, efficacy, tolerability and convenience. Due to our
significant experience in deuterium chemistry and pharmaceutical research and development, we believe
we are well-positioned to efficiently identify compounds that can benefit from deuterium substitution
and create optimally deuterated product candidates.

We have a robust pipeline, including clinical-stage candidates and a number of preclinical compounds that we are actively developing. View Concert’s product pipeline.

CTP-354 - Potentially First-in-Class Non-Sedating Treatment for Spasticity

CTP-354 is a novel, potentially first-in-class, non-sedating treatment for spasticity that we are initially developing for use in both patients with spinal cord injury and multiple sclerosis. CTP-354 is a
subtype selective GABA(A) receptor modulator. GABA(A) receptors are found in the nervous system and,
when activated, reduce the transmission of certain nerve signals. Subtype selective GABA(A) modulators have the potential to retain the known therapeutic effects of benzodiazepines including anti-spasticity, muscle relaxation, anti-anxiety, anti-seizure and potentially anti-pain activities.  Benzodiazepines, which include well-known drugs such as Valium® (diazepam) and some sleep agents such as zolpidem (Ambien®) and zaleplon (Sonata®), exert their effect non-selectively across the GABA(A) receptors. However, their use is often limited by undesirable effects such as sedation and ataxia. CTP-354 lacks agonist activity at the specific GABA(A) receptor subtype associated with those side effects. 

CTP-354 is currently in Phase 1 clinical testing.

About Spasticity

Spasticity is a chronic condition characterized by involuntary tightness, stiffness or contraction of
muscles that occurs in patients who have damage to the brain or spinal cord. Spasticity can result from a
wide range of disorders, including multiple sclerosis, spinal cord injury, cerebral palsy, amyotrophic
lateral sclerosis, stroke and hereditary spastic paraplegia. Symptoms can range from mild muscle
tightness to more severe symptoms, including crippling and painful inability to move limbs that can
result in disability and diminished quality of life. The American Association of Neurological Surgeons
estimated in 2006 that there were 12 million patients suffering from spasticity worldwide.

According to the National Spinal Cord Injury Statistics Center, in 2012, there were approximately 270,000 people in the United States suffering from spinal cord injury with approximately 12,000 new incidences per year. According to a 2011 report of the University of Washington Model Systems Knowledge Translation Center, 65% to 78% of spinal cord injury patients experience some degree of spasticity. Based on articles published in Archives of Physical Medicine and Rehabilitation in 1990 and 1999, Concert estimates that 28% to 46% of spinal cord injury patients suffer from problematic spasticity that could result in treatment.

According to American Association of Neurological Surgeons, about 80% of people with multiple sclerosis suffer from some degree of spasticity. Of the estimated 400,000 patients diagnosed with multiple sclerosis in the United States, Concert estimates that at least 34%, or 140,000 patients, suffer from moderate to severe spasticity that impacts daily function in a meaningful way.

CTP-499 - Potentially First-in-Class Treatment for Diabetic Nephropathy

CTP-499 is a novel, potentially first-in-class, treatment for diabetic nephropathy in patients with type 2 diabetes that we are developing as an additive treatment to the current standard of care. CTP-499 is a multi-subtype selective inhibitor of phosphodiesterases, or PDEs, which are enzymes that we believe play an important role in diabetic nephropathy.

We are currently conducting the final, open-label portion of a three-part Phase 2 clinical trial of CTP-499 in which we have enrolled patients with type 2 diabetic nephropathy and macroalbuminuria.

About Diabetic Nephropathy

Diabetic Nephropathy is a condition in which the kidneys’ ability to filter blood is impaired and
is typically chronic and progressive.

According to the Centers for Disease Control, in 2011, approximately 26 million people in the
United States had diabetes, with 90% to 95% suffering from type 2 diabetes, commonly referred to as
adult-onset diabetes. According to a 2009 article in the American Diabetes Association journal Diabetes
Care, type 2 diabetes is the leading cause of chronic kidney disease. The United States Renal Data Survey,
a national data system that collects, analyzes and distributes information about end-stage renal disease,
the most severe stage of chronic kidney disease, in the United States, indicates that diabetes is the leading cause of end-stage renal disease in the United States. Patients with type 2 diabetes and chronic kidney disease have a markedly increased mortality rate compared to type 2 diabetics without chronic kidney disease.

Other Pipeline Programs

  • AVP-786, a combination of a deuterium-substituted dextromethorphan analog and an ultra-low dose of quinidine. We have granted Avanir an exclusive license to develop and commercialize deuterated dextromethorphan analogs, including the analog in AVP-786. Avanir is developing AVP-786 for the treatment of neurologic and psychiatric disorders. In February 2013, Avanir reported positive results from a Phase 1 clinical trial of AVP-786. In July 2014, Avanir reported plans to advance AVP-786 into a Phase 2 clinical trial in the third quarter of 2014 for the adjunctive treatment of major depressive disorder.
  • A collaboration with Jazz Pharmaceuticals to research, develop and commercialize JZP-386, a product candidate containing a deuterated analog of sodium oxybate for potential use in patients with narcolepsy. Sodium oxybate is the active ingredient in the marketed drug Xyrem. In July 2014, Concert and Jazz Pharmaceuticals announced the initiation of the Phase 1 clinical trial of JZP-386.
  • A collaboration with Celgene to research, develop and commercialize certain deuterated compounds for the treatment of cancer or inflammation, with an initial focus on a single program. In the initial program, we have selected CTP-730, a product candidate for the treatment of inflammatory diseases, and expect to begin clinical trials in 2014.

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Intellectual Property Summary

We protect our product candidates through the use of patents, trade secrets and careful monitoring of
our proprietary know-how. Our patent portfolios are wholly owned by us. They include issued patents or patent applications that claim deuterated analogs of more than 90 non-deuterated drugs and drug candidates. View list of U.S. Issued Patents.

Scientific Presentations

Concert has presented scientific findings at a number of scientific and medical conferences. View Concert's recent poster presentations

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