Company: NCEL
Filing Date: 2025-05-16
Form Type: 20-F
Source: 0001213900-25-044868
Chunk: 181

Company: NewcelX Ltd.
Filing Date: 2025-05-16
Form: 20-F
Item: Item 4
Chunk 181
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 history, and are associated with peripheral vasculopathy, including Raynaud’s phenomenon.
CII stimulants are also sleep-affecting drugs 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-term use 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-on of 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-optimal efficacy 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-limiting adverse 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-stimulant treatments available,
such as atomoxetine (Strattera®), clonidine (Kapvay®), and guanfacine (Intuniv®), that were
developed to address this need; however, their efficacy is sub-optimal to 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-stimulant treatment 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 stim