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Nat Sci Sleep. 2015; 7:51 -61. Unmet needs of patients with narcolepsy: perspectives on emerging treatment options PMC (nih.gov) 2. Safety Overview of Post marketing and Clinical Experience of Sodium Oxybate (Xyrem): Abuse, Misuse, Dependence, and Diversion - PMC (nih.gov) 3. Unmet needs of patients with narcolepsy: perspectives on emerging treatment options - PMC (nih.gov) 2023 Supernus Pharmaceuticals, Inc.
Parent and Major Metabolites have NET, DAT & SERT Activity SPN-443 and its metabolites all bind to and inhibit NET, DAT, and SERT but with varying potencies Metabolites could provide longer duration of effect Functional Assay Transporters (IC50 in nM) SPN-443 Metabolite 1 Metabolite 2 NET 12 0.52 53 DAT 110 12 63 SERT 1200 680 1200 In vitro Binding Assay (Ki in nM) SPN-443 Metabolite 1 Metabolite 2 NET 25 0.71 270 DAT 120 6 10 SERT 670 40 110 MOP 280 160 >10000 Affinity (human isoforms) Functional Activity (human isoforms) 89 2023 Supernus Pharmaceuticals, Inc.
SPN-817: Current MoA Hypothesis for Seizure Control: Cholinergic Modulation of Neuronal Excitation Seizures are the result of the imbalance of the Excitation/Inhibition (E/I) ratio in susceptible regions of the brain Acetylcholine augmentation activates cholinergic pathways in different cellular types in the brain to restore E/I balance 71 Ach Activation of Ach receptors located on inhibitory interneurons, excitatory neurons, and glial cells Excitation/ Inhibition Restoration of E/I balance Seizure control AChE Inhibition 71 2023 Supernus Pharmaceuticals, Inc.
Efficacy is most important Efficacy is the single-most important motivator in driving treatment choice, followed by safety / drug interactions. Adoption is driven by adult treaters Pediatric treaters are more cautious and slower to adopt. 1 Supernus Conjoint Market Research Study (June 2023) 65 Adult and pediatric treaters see value in pro-cognitive and neuroprotection benefits 2023 Supernus Pharmaceuticals, Inc.
IQVIA Integrated NPA + NMTA, MAT April 2023 Refractory Focal Seizures (40%) 6.9M TRx Focal Seizures2 17.2M TRx Focal seizures represent 60% of all epilepsy/seizure disorder TRx Includes drugs that treat non-seizure disorders as well (e.g., gabapentin/neuropathic pain, lamotrigine/bipolar, etc.) US Market- $2.7B GlobalData Net Revenue Sept 2023 64 2023 Supernus Pharmaceuticals, Inc.
Moving towards molecules that can impact neuroplasticity Development of psychedelics is prevalent; however, they have significant AEs and intensive therapy will be required for use Could differentiate by remodeling neurological synapses to facilitate lasting benefits Anticipated to be a $5B market1 25 1 GlobalData Forecast 2029, Projected Combined Psychedelic Brands DSST: Digit Symbol Substitution Test 2023 Supernus Pharmaceuticals, Inc.
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