Company: NCEL
Filing Date: 2025-03-31
Form Type: F-4/A
Source: 0001213900-25-026428
Chunk: 708

Company: NewcelX Ltd.
Filing Date: 2025-03-31
Form: F-4/A
Chunk 708
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 are also sleep -affectingdrugs and shorten total sleep time, increase the time it takes to fall asleep, adversely impact the ability to stay asleep, and increase daytime sleepiness. The long -termuse of prescription stimulants has been widely reported to cause drug tolerance, which is the loss of efficacy over time and requires a complete change in treatment, or an increased dose of the existing treatment, or the add -onof another medication to the existing treatment in order to achieve therapeutic effectiveness. This leads to an increased risk of developing serious adverse effects that are unrelated to ADHD. Another concern in treating patients with CII stimulants is the potential “rebound effect” that occurs when the medication wears off, resulting in the return of ADHD symptoms and which may also occur in an amplified form. In children especially, this often triggers increased irritability and/or aggressive behavior and the rebound in children and adults may be exacerbated by multiple drug administrations, often used to obtain the desired duration of effect or to address drug tolerance. Additionally, studies have highlighted that primary limitations of CII stimulants are intolerable adverse effects that interfere with patient adherence rates and sub -optimalefficacy with the onset of drug tolerance. According to the 2002 practice parameter for the use of stimulant medications from the American Academy of Child & Adolescent Psychiatry, approximately 30% of patients do not respond adequately to or have dose -limitingadverse effects with CII stimulants. Additionally, certain patients, or parents of patients, prefer not to use CII stimulants due to their stigma and known abuse potential. There are a few non -stimulanttreatments available, such as atomoxetine (Strattera ®), clonidine (Kapvay ®), and guanfacine (Intuniv ®), that were developed to address this need; however, their efficacy is sub -optimalto stimulants and while unscheduled, their overall safety profile does not necessarily provide an improvement to CII stimulants. Strattera, a norepinephrine reuptake inhibitor, was the first non -stimulanttreatment option for ADHD and while its initial launch started strong, underscoring the demand for an alternative to CII stimulants, sales steadily declined as patients and physicians found it to not be nearly as effective as CII stimulants. It is now considered a second -linetreatment and is typically used as an alternative to CII stimulants for patients who have a