Zalvari (molindone XR) / Supernus Pharma - LARVOL DELTA

Exploratory fMRI Study on the Treatment for Impulsive Aggression in Children With ADHD (clinicaltrials.gov) - P2 | N=7 | Terminated | Sponsor: Supernus Pharmaceuticals, Inc. | N=14 ➔ 7

Enrollment change • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Treatment of Impulsive Aggression in Subjects With ADHD in Conjunction With Standard ADHD Treatment (CHIME 4) (clinicaltrials.gov) - P3 | N=491 | Terminated | Sponsor: Supernus Pharmaceuticals, Inc. | Completed ➔ Terminated; The program was shut down due to a lack of efficacy.

Trial termination • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Pediatrics • Psychiatry

Treatment of Impulsive Aggression (IA) in Adolescent With ADHD in Conjunction With Standard ADHD Treatment (clinicaltrials.gov) - P3 | N=41 | Terminated | Sponsor: Supernus Pharmaceuticals, Inc. | N=186 ➔ 41

Enrollment change • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Treatment of Impulsive Aggression (IA) in Adolescent With ADHD in Conjunction With Standard ADHD Treatment (clinicaltrials.gov) - P3; N=186; Terminated; Sponsor: Supernus Pharmaceuticals, Inc.; Trial completion date: Dec 2021 ➔ Jan 2020; Recruiting ➔ Terminated; Trial primary completion date: Jul 2020 ➔ Jan 2020; Financial decision

Clinical • Trial completion date • Trial primary completion date • Trial termination • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Treatment of Impulsive Aggression in Subjects With ADHD in Conjunction With Standard ADHD Treatment (CHIME 4) (clinicaltrials.gov) - P3; N=491; Completed; Sponsor: Supernus Pharmaceuticals, Inc.; Recruiting ➔ Completed

Clinical • Trial completion • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Beyond stimulants: a systematic review of randomised controlled trials assessing novel compounds for ADHD. (PubMed, Expert Rev Neurother) - "Expert opinion: The authors found 28 pertinent RCTs of compounds acting on a variety of biological targets, including Dasotraline, Viloxazine (SPN-812), Centanafadine SR (CTN SR), OPC-64005, Fasoracetam (NFC-1, AEVI-001), Metadoxine (MDX), Vortioxetine, Tipepidine Hibenzate, Oxytocin, Sativex (delta-9-tetrahydrocannabinol (THC) plus cannabidiol), Mazindol, and Molindone hydrochloride (SPN-810)...However, they may offer comparable or better tolerability. Additionally, agents acting on etiopathophysiological targets disrupted in specific subgroups of patients with ADHD will move forward the pharmacotherapy of ADHD from a "one size fits all" to a "precision medicine" approach."

Clinical • Journal • Review • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Long-Term Efficacy and Safety of Extended-Release Molindone (SPN-810) to Manage Impulsive Aggression in Children With Attention-Deficit/Hyperactivity Disorder (ASCP 2017) - "Improvements in patients with IA behavior achieved with SPN-810 treatment (R-MOAS change from DB baseline) were sustained during OLE treatment (stable R-MOAS score from OLE baseline). SPN-810 was generally well tolerated, and there was a relatively low rate of discontinuation due to AEs. AEs were consistent with the types of events expected in children receiving low-dose SPN-810 added to ADHD medication."

Retrospective data • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Biosimilar • CNS Disorders

Supernus: Q2 FY 2016 Results (Supernus Pharmaceuticals) - Anticipated launch for IA-ADHD in 2019; Anticipated completion of enrollment in Phase 3 trials CHIME 1 (NCT02618408) and CHIME 2 (NCT02618434) for IA-ADHD in 2017

Anticipated enrollment status • Anticipated launch • ADHD (Impulsive Aggression) • CNS Disorders

A Double-Blind, Randomized Study of Extended-Release Molindone for Impulsive Aggression in ADHD. (PubMed, J Atten Disord) - " These results suggest SPN-810 may be effective in reducing residual IA behaviors in children with ADHD. Research is still needed to support the benefit-risk profile of SPN-810 in pediatric populations."

Clinical • Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Pediatrics

Supernus Announces Fourth Quarter and Full Year 2019 Financial Results (GlobeNewswire, Supernus Pharmaceuticals, Inc.) - "SPN-812: The Company expects to complete enrollment in the ongoing Phase III program in adult patients by the end of 2020. SPN-810: Phase III P302 trial in patients 6 to 11 years old did not meet its primary endpoint....The Company will halt all development activities on SPN-810 in IA....We continue to prepare the Company for the commercial launch of SPN-812...Research and development (R&D) expenses for full year 2019 were $69.1 million, lower than the $89.2 million in 2018...These reductions were partially offset by SPN-812 manufacturing costs in 2019 to support the Company’s NDA submission."

Commercial • Discontinued • Enrollment status • P3 data

Supernus provides update on results from phase III study (P301) of SPN-810 for treatment of impulsive aggression (IA) in ADHD patients (GlobeNewswire) - P3, N=333; CHIME 1 (NCT02618408); Sponsor: Supernus; "Supernus Pharmaceuticals...is providing an update on the results from the first Phase III study (P301) of SPN-810, a novel treatment of Impulsive Aggression (IA) in patients with ADHD....The Company plans on finalizing the statistical plan (SAP) for the second Phase III P302 study in patients 6 to 11 years old taking into consideration the exclusion of patients with 6 or less episodes of IA per week. The Company will be submitting the SAP to the Food and Drug Administration (FDA) and expects data from the P302 study in the first quarter of 2020."

P3 data: top line • Regulatory

Treatment of Impulsive Aggression in Subjects With ADHD in Conjunction With Standard ADHD Treatment (CHIME 1) (clinicaltrials.gov) - P3; N=333; Completed; Sponsor: Supernus Pharmaceuticals, Inc.; Recruiting ➔ Completed; Trial completion date: Apr 2020 ➔ Sep 2019

Clinical • Trial completion • Trial completion date

Treatment of Impulsive Aggression in Subjects With ADHD in Conjunction With Standard ADHD Treatment (CHIME 2) (clinicaltrials.gov) - P3; N=297; Completed; Sponsor: Supernus Pharmaceuticals, Inc.; Recruiting ➔ Completed; Trial primary completion date: May 2018 ➔ Nov 2019

Clinical • Trial completion • Trial primary completion date

Exploratory fMRI Study on the Treatment for Impulsive Aggression in Children With ADHD (clinicaltrials.gov) - P2; N=14; Terminated; Sponsor: Supernus Pharmaceuticals, Inc.; N=30 ➔ 14; Trial completion date: Mar 2020 ➔ Nov 2019; Recruiting ➔ Terminated; Trial primary completion date: Mar 2020 ➔ Nov 2019; Financial decision

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial termination

Treatment of Impulsive Aggression (IA) in Adolescent With ADHD in Conjunction With Standard ADHD Treatment (clinicaltrials.gov) - P3; N=186; Recruiting; Sponsor: Supernus Pharmaceuticals, Inc.; Trial completion date: Dec 2019 ➔ Dec 2021; Trial primary completion date: Jul 2019 ➔ Jul 2020

Clinical • Trial completion date • Trial primary completion date

Supernus announces third quarter 2019 financial results and topline data from phase III study of SPN-810 for treatment of impulsive aggression (IA) in ADHD patients (Yahoo Finance) - "Phase III P301 trial in patients 6 to 11 years old did not meet its primary endpoint....Enrollment in the Phase III P302 trial in patients 6 to 11 years old is at 98% of the target. The Company will cease enrollment in the P302 trial and analyze the data, which are expected to be available by the end of 2019. In the meantime, enrollment in the P503 Phase III trial (adolescents) is on hold until data from the P302 study are available and a final decision is reached regarding the SPN-810 program in IA."

Enrollment status • P3 data

Supernus announces second quarter 2019 financial results (GlobeNewswire) - "SPN-810 - Novel treatment of Impulsive Aggression in patients with ADHD... Enrollment in the Phase III P301 trial is complete, with data expected in the fourth quarter of 2019....Enrollment in the Phase III P302 trial continues, with data now expected in the first quarter of 2020....Enrollment in the open label extension (OLE) study continues at 90% or higher."

Enrollment status • P3 data

Exploratory fMRI Study on the Treatment for Impulsive Aggression in Children With ADHD (clinicaltrials.gov) - P2; N=30; Recruiting; Sponsor: Supernus Pharmaceuticals, Inc.; Not yet recruiting ➔ Recruiting; Trial completion date: Dec 2019 ➔ Mar 2020; Trial primary completion date: Dec 2019 ➔ Mar 2020

Clinical • Enrollment open • Trial completion date • Trial primary completion date

SPN-810: Data from P3 trial (NCT03597503) in adolescents diagnosed with ADHD in 2020 (Supernus Pharmaceuticals) - Investor Presentation

P3 data

SPN-810: NDA filing for impulsive aggression in H2 2020 (Supernus Pharmaceuticals) - Investor Presentation

NDA

Supernus announces first quarter 2019 financial results (GlobeNewswire) - "SPN-810 – Novel treatment of Impulsive Aggression in patients with ADHD...Enrollment in the Phase III trials (P301 and P302) continues with data from both trials expected in the second half of 2019....The Company continues to expect to submit an NDA for SPN-810 in the second half of 2020, and to launch it, pending FDA approval, in the second half of 2021....Patient dosing continues in the Phase III trial (P503) in adolescent patients."

Enrollment status • Launch US • NDA • P3 data

Treatment of Impulsive Aggression in Subjects With ADHD in Conjunction With Standard ADHD Treatment (CHIME 4) (clinicaltrials.gov) - P3; N=400; Recruiting; Sponsor: Supernus Pharmaceuticals, Inc.; Trial primary completion date: Mar 2019 ➔ Mar 2020

Clinical • Trial primary completion date

Treatment of Impulsive Aggression in Subjects With ADHD in Conjunction With Standard ADHD Treatment (CHIME 1) (clinicaltrials.gov) - P3; N=291; Recruiting; Sponsor: Supernus Pharmaceuticals, Inc.; Trial primary completion date: Mar 2018 ➔ Oct 2019

Clinical • Trial primary completion date

A proposed anti-maladaptive aggression agent classification: improving our approach to treating impulsive aggression. (PubMed, Postgrad Med) - "Based on these studies we will review how SPN-810 may be well suited for a new, anti-maladaptive aggression drug class and more precisely, a proposed subgroup of IA modulators. The goal of this review is to begin improving the identification of and therapeutic approach for maladaptive aggression as well as IA through more precise anti-maladaptive aggression agent categorization."

Journal • Review

Exploratory fMRI Study on the Treatment for Impulsive Aggression in Children With ADHD (clinicaltrials.gov) - P2; N=30; Not yet recruiting; Sponsor: Supernus Pharmaceuticals, Inc.; Trial completion date: Dec 2018 ➔ Dec 2019; Initiation date: Sep 2018 ➔ May 2019; Trial primary completion date: Dec 2018 ➔ Dec 2019

Clinical • Trial completion date • Trial initiation date • Trial primary completion date