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Appello Pharmaceuticals Begins Phase 1 Clinical Trial


Trial advances research of the Parkinson’s disease treatment

Nashville, TN (10/4) -- Appello Pharmaceuticals, Inc., a clinical-stage pharmaceutical company committed to addressing the needs of people suffering from disorders of the nervous system, today announced that dosing has commenced in the company’s Phase 1 dose-escalation study of its lead drug candidate, AP-472. Originally developed at Vanderbilt University’s Warren Center for Neuroscience Drug Discovery (WCNDD) with funding from the National Institutes of Health and the Michael J. Fox Foundation, among others, AP-472 is intended for the treatment of Parkinson’s disease. AP-472 is a highly selective, small molecule, positive allosteric modulator of the metabotropic glutamate receptor subtype 4, or an “mGlu4 PAM.”


“Moving forward with the clinical trial is the next critical step in advancing AP-472 to help people with Parkinson’s disease. It has taken nearly 20 years of work to achieve this moment and we are so grateful for all our partners and colleagues at WCNDD who have worked tirelessly to get to this point,” said Brian Laden, Ph.D., President and CEO of Appello.


The Phase 1 study is a randomized, double-blind, placebo-controlled trial, being conducted in healthy young, middle-aged, and elderly adults, to evaluate the safety, tolerability, and pharmacokinetics of AP-472. The study is enrolling subjects at Worldwide Clinical Trials in San Antonio, Texas. Subjects in each cohort are randomized to receive either AP-472 or placebo. Appello Pharmaceuticals plans to use the findings from the Phase 1 study to inform dose selection for its Phase 1b and Phase 2 clinical studies in people with Parkinson’s disease.


An estimated 1 million Americans have Parkinson’s disease, a progressive brain disorder characterized by resting tremor, rigidity, and slowness of movement, as well as non-motor symptoms. It is caused by the death of nerve cells in a specific brain region that produce the neurotransmitter dopamine.


“It is exciting to see a highly specific and potent mGlu4 PAM tested in the clinic. This class of drugs has great potential to significantly improve the lives of Parkinson’s disease patients,” said Dr. David Standaert, John N. Whitaker Professor and Chair of Neurology, University of Alabama at Birmingham.


Dopamine replacement therapies, such as levodopa, continue to be the mainstay of treatment for Parkinson’s disease. Levodopa relieves many of the symptoms of the disease, but over time it can cause uncontrollable involuntary movements called dyskinesias and other debilitating side effects.


“Patients need a drug that works in a fundamentally different way from dopamine replacement therapy. That is what AP-472 does,” said Dr. Robert Elfont, CMO at Appello.


The mGlu4 PAM AP-472 is intended to work in conjunction with levodopa to increase the amount of time during the day that people will have relief from their Parkinson’s disease symptoms without experiencing troublesome dyskinesias.


“Parkinson’s disease patients have a tremendous need for new drugs to improve their symptoms at the point when levodopa-based drugs are no longer effective on their own,” said Dr. Rajesh Pahwa, Professor of Neurology and Director of the Parkinson’s Disease and Movement Disorder Center, University of Kansas Medical Center.


About mGlu4 and AP-472
mGlu4 is one of a large family of G-protein coupled receptors (GPCRs) that binds glutamate and modulates its signaling. Being an mGlu4 PAM, AP-472 potentiates the effects of glutamate binding at the mGlu4 receptor. As Parkinson’s disease progresses, the persistent reduction in dopamine levels results in a dysregulation of glutamate signaling in critical circuitry within the brain.


Preclinical and clinical evidence suggests that activation of the mGlu4 receptor results in restoration of balanced signaling through the two neural pathways in a region of the brain that controls movement. When given systemically in preclinical models of Parkinson’s disease, AP-472 reached the brain and relieved motor symptoms, including rigidity and immobility. Its effects were augmented when administered in conjunction with levodopa.


About Appello Pharmaceuticals, Inc.
Appello Pharmaceuticals, Inc. is a clinical-stage therapeutics company focused on identifying and developing innovative early-stage drug candidates for patients living with disorders of the nervous system. Based in Nashville, Tennessee, Appello has a strong collaborative relationship with Vanderbilt University’s Warren Center for Neuroscience Drug Discovery (WCNDD), where AP-472 was discovered.

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