Company: NCEL
Filing Date: 2025-06-09
Form Type: F-4/A
Source: 0001213900-25-052354
Chunk: 322

Company: NewcelX Ltd.
Filing Date: 2025-06-09
Form: F-4/A
Chunk 322
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 symptoms of narcolepsy, EDS and cataplexy. • Quilience is expected to have minimal drug interactions.Based on the results of five in vitro metabolism studies, Mazindol ER has a very low potential for drug interactions In the lab, mazindol did not interact with any of the enzymes that metabolize drugs in humans. Its metabolism was also not influenced by any well -knownenzyme inhibitors or stimulants. One of its metabolites (representing less than 12% of mazindol) showed some interactions with a minor metabolic enzyme named P -glycoprotein(Pgp) and this interaction will be further investigated in humans. Nevertheless, mazindol showed significantly less interactions with metabolic enzymes than any other narcolepsy treatment. 164 • Quilience is being developed as a once -daily oral tablet administered in the morning upon wakening. Patients have identified a need for treatment options that are easier to take, dosed less frequently, do not disrupt night -timesleeping and provide full day coverage of symptoms. NLS believes that once -dailydosing with Quilience may address this need and may help improve patient compliance and adherence with treatment. Quilience utilizes NLS’s proprietary extended -releaseformulation and is being designed to optimize its pharmacokinetic and pharmacodynamic properties with a rapid onset of action and prolonged controlled therapeutic effect, allowing for a daily oral dose that effectively provides consistent and long -actingsymptom control to uniquely meet the needs of patients. Leveraging its scientific insights and direct hands -onclinical experience, NLS is developing compounds that it believes have innovative mechanisms of action with positive therapeutic profiles and represent a differentiated treatment option to overcome the limitations of the current therapies. For example, Quilience and Nolazol are agents that differ significantly from available treatments in their apparent dual mechanism of action. In addition to their action as a triple monoamine reuptake inhibitor that blocks serotonin, norepinephrine, and dopamine transporters, they also target the orexin pathway as a selective (in relation to the orexin -1receptor) partial agonist of the OX2R. This activity could provide cortical regulation of the lower brain, and thereby lead to improved attention and inhibitory control, while also improving regulation of executive function and inhibitory control which would provide both “top down” and “bottom up” regulation of the brain. Orexin neurons (located in a part of the brain known as the hypothalamus) are