Q&A: SK Life Science and the central nervous system

SK Life Science (SKLSI) is a subsidiary of SK Biopharmaceuticals Co., Ltd., focused on developing and bringing to market treatments for disorders of the central nervous system (CNS). SKLSI believes there is significant unmet need for patients with CNS disorders, particularly epilepsy. Despite the addition of several new treatment options over the past five years, approximately one-third of the epilepsy patient population continues to have seizures. Even more troubling is the fact that this one-third figure has remained relatively constant over the past several decades.

The SKLSI team says it is firmly committed to making a difference in the lives of people suffering from epilepsy, and its lead compound, cenobamate (YKP3089), is currently being evaluated as a potential treatment of adults with partial-onset seizures. SKLSI has a pipeline of six products in development for the treatment of CNS disorders, including epilepsy, sleep disorder and attention deficit hyperactivity disorder (ADHD). Dr. Marc Kamin, vice president and chief medical officer of SKLSI, spoke with us about SKLSI, CNS disorders and several of the compounds in the SKLSI pipeline.

Marc Kamin, M.D.: Established in 1993, SKLSI was created as a subsidiary of SK Biopharmaceuticals, Co. Ltd., focused on developing and commercializing treatments for disorders of the central nervous system. Both companies are a part of the global conglomerate SK Group, the second largest company in South Korea, SK Group, which generated more than $108 billion in revenue in 2016.

Kamin: SKLSI, which is based in South Korea, announced the launch of its commercial corporate presence and infrastructure in the U.S. in November 2017. Its U.S. headquarters are currently located in Fair Lawn, N.J. By establishing a U.S. footprint, the company has strategically increased its flexibility in how it approaches commercializing products and forming business partnerships.

Leadership in the U.S. and Korea collaborate every day to ensure employees are united on all projects. The company has leveraged its global experience to rapidly build its U.S. clinical and commercial infrastructure. SKLSI currently has more than 70 people with decades of experience researching and commercializing drugs in the states, and plans to continue expanding this workforce in 2018 and beyond as it moves toward the approval and launch of the late-stage products in the pipeline.

Kamin: The brain remains one of the most mysterious organs in the human body, and much of the underlying biology of neurological disease remains uncertain. These complexities and continuing unmet needs fuel the company’s commitment to and interest in finding novel therapeutic solutions for epilepsy, attention deficit hyperactivity disorders and sleep disorders. While many companies have decreased research and development efforts in this space, SK life science is dedicated to finding solutions for the millions of patients who need effective and safe treatments.

One of the largest unmet needs in CNS disorders is for epilepsy. As many as 3.4 million people live with epilepsy in the U.S. According to the Centers for Disease Control and Prevention (CDC), only 44 percent of respondents with active epilepsy on epilepsy medication were seizure-free in the past year. Furthermore, from 2000-2012, the number of patients who achieved seizure freedom after three or more drugs has barely changed.

SKLSI has a pipeline of six products across these categories and initiated 16 Investigational New Drug (IND) applications with the U.S. Food and Drug Administration (FDA). The company also has a highly blood-brain, barrier-permeable, unique compound library and translational screening system which has been clinically proven in the field of CNS disorders over the past 20 years.

Kamin: Cenobamate (YKP3089) is an investigational compound being evaluated as a potential treatment option for adult patients with partial-onset seizures. It is the company’s lead product and largest focus area. A pivotal Phase 3 trial is underway, and SKLSI expects to file a new drug application with the FDA as early as late 2018.

The potential approval of cenobamate would represent a historic milestone for SK Life Science and mark its planned transformation into a global, fully integrated pharmaceutical company. SK Life Science expects to independently market and sell the drug without out-licensing the asset.

Kamin: Although both compounds are in the carbamate family, they are structurally quite different. Cenobamate has two ring moieties as opposed to carisbamate, which has one. Studies in partial seizures with carisbamate demonstrated modest efficacy, whereas studies with cenobamate demonstrated some of the best efficacy results seen for partial seizures. Finally, the seizure-free rates demonstrated with cenobamate far exceed those found with carisbamate.

Kamin: In March 2018, the FDA accepted for filing with standard review the company’s New Drug Application seeking marketing approval for solriamfetol (JZP-110), an investigational medicine for the treatment of excessive sleepiness in adult patients with narcolepsy or obstructive sleep apnea (OSA). The PDUFA goal date for an FDA decision is December 20, 2018.

Solriamfetol (JZP-110) is a selective dopamine and norepinephrine reuptake inhibitor. The solriamfetol Phase 3 clinical program includes one study evaluating excessive sleepiness in adult patients with narcolepsy (TONES 2), two studies evaluating excessive sleepiness in adult patients with OSA (TONES 3 and TONES 4), and an open-label, long-term safety and maintenance of efficacy study (TONES 5) in the treatment of excessive sleepiness in patients with narcolepsy or OSA.

Jazz Pharmaceuticals has worldwide development, manufacturing, and commercialization rights to solriamfetol, excluding certain jurisdictions in Asia. SK Biopharmaceuticals, the discoverer of the compound (also known as SKL-N05), maintains rights in 12 Asian markets, including Korea, China and Japan. Solriamfetol has orphan drug designation in the United States for narcolepsy.

Kamin: The development of two of our early phase candidates—SKL13865, for the possible treatment of ADHD, and YKP10461, for the possible treatment of Parkinson’s disease—is consistent with our company’s objective to be a leader in the CNS community by working to develop products in all areas of this disease category. We look forward to providing more details on these Phase I products as development continues.

Kamin: This compound has a novel mechanism of action. The most typical treatments for schizophrenia are antipsychotics, which act on dopamine and serotonin receptors, and control mainly positive symptoms such as delusions and hallucinations. In addition to positive symptoms, there are also a number of negative symptoms (e.g. blunted affect, apathy, anhedonia, lack of motivation, etc.) along with cognitive impairment that are not well controlled by antipsychotic use alone.

SKL20540 is an mGluR5 PAM, which works to indirectly modulate the NMDA receptor, which is thought to be a key player in schizophrenia and more specifically, cognitive impairment and negative symptoms. Examples of cognitive impairment include poor memory, attention, reasoning and processing. In preclinical models for negative symptoms, SKL20540 showed significant improvement in social interaction time. In rodent models of recognition memory the results showed significant anti-amnesic effects. Additionally, based on preclinical testing, there does not appear to be an effect on the positive symptom efficacy of three major antipsychotics (risperidone, olanzapine and aripiprazole), which means that SKL20540 can be safely used as adjunctive therapy.

Kamin: SK Life Science believes its experience and development expertise gives it the unique opportunity to succeed and provide new options for patients. By being part of the SK family of companies, SK Life Science has the business structure of an integrated, global biopharmaceutical company capable of seamlessly bridging from the development of clinical assets to commercializing them.