Company: NCEL
Filing Date: 2025-01-28
Form Type: 425
Source: 0001213900-25-007315
Chunk: 2

Company: NewcelX Ltd.
Filing Date: 2025-01-28
Form: 425
Chunk 2
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| ● | Mu-opioid receptor (“MOP”) interaction: Provides partial modulation                                     
 of opioid effects, potentially reducing cravings and withdrawal symptoms without reinforcing addiction. |

| ● | Orexin-2 receptor (“OX2R”) partial agonist: Aids in restoring                                                    
 sleep-wake cycles and enhancing cognitive stability, which are significantly disrupted during opioid withdrawal. |

Scientific Rationale
Fentanyl, a synthetic opioid that is up to 50 times more potent than heroin, has driven a global health crisis due to its high abuse potential
and severe withdrawal symptoms. Traditional treatments, such as methadone and buprenorphine, often come with limitations, including risk
of dependence and regulatory hurdles.

Mazindol ER offers a potential non-opioid alternative, addressing the
underlying neurochemical imbalances associated with fentanyl addiction while supporting recovery through its multimodal action on neurotransmitter
systems. The sustained-release formulation provides a long-acting therapeutic effect, improving patient compliance and minimizing withdrawal-related
disruptions.

Mechanism of Action of Mazindol ER
Mazindol’s unique pharmacodynamic properties position it as a promising candidate for opioid dependence treatment. Its mechanisms
include:

| ● | Inhibition of dopamine and norepinephrine transporters, restoring neurochemical 
 balance and reducing cravings.                                                  |

| ● | 5-HT1A receptor modulation, potentially alleviating anxiety and depressive 
 symptoms associated with withdrawal.                                       |

| ● | MOP agonist activity, which may help mitigate opioid withdrawal symptoms 
 while preventing full opioid reinforcement.                              |

| ● | Partial OX2R agonist activity, aiding in circadian rhythm regulation and 
 reducing the impact of opioid-induced sleep disturbances.                |

Preclinical Study Objectives and Next Steps

The preclinical study, designated Study KO-943, will focus on:

| 1. | Evaluating the safety and efficacy of Mazindol ER in fentanyl dependence models. |

| 2. | Assessing pharmacokinetics and pharmacodynamics in opioid-exposed subjects. |

| 3. | Exploring the impact of Mazindol ER on craving reduction, withdrawal mitigation, and cognitive performance. |

The study is expected to be completed within 12-18 months. Upon successful
results, NLS will potentially seek regulatory pathways to advance to clinical development.

"We believe that Mazindol ER could offer a paradigm shift in opioid
addiction treatment," added Dr. Konofal, M.D./PhD, Chief