DATA FROM NOVEL, EXPLORATORY ANALYSIS OF INTERMITTENT VALTOCO® (DIAZEPAM NASAL SPRAY) CIV USE INDICATES MORE THAN TWO-FOLD INCREASE IN MEAN INTERVAL BETWEEN SEIZURE CLUSTERS

• Neurelis presents two posters at the 2^nd North American Epilepsy Congress (NAEC) highlighting new analysis of change in timing between seizure clusters across 12 months, and final effectiveness and safety data from the Phase 3, open-label, repeat-dose study of VALTOCO

SAN DIEGO, May 5, 2022 /PRNewswire/ -- Neurelis, Inc., today announced findings from a novel, exploratory analysis of VALTOCO® (diazepam nasal spray). The data indicates that patients using the therapy had a significant increase in the time between their seizure clusters, or SEIzure InterVAL data (SEIVAL) over a 12-month period. VALTOCO is approved for the acute treatment of episodes of frequent seizure activity (i.e., seizure clusters). This investigational data) will be presented at the 2^nd NAEC, held virtually May 5-8, 2022.

An additional poster summarizes final results on the use of second doses, safety, and retention rate from the completed long-term, open-label, repeat-dose safety study of VALTOCO for the treatment of seizure clusters in patients with epilepsy ages 6 to 65. VALTOCO, a nasal spray for acute treatment of episodes of frequent seizure activity in adult and pediatric patients 6 years of age and older, was approved by the U.S. Food and Drug Administration (FDA) in 2020.

"VALTOCO and other rescue therapies play a critical role in treatment plans for people with poorly controlled epilepsy and seizure clusters," said Adrian Rabinowicz, M.D., SVP Clinical Development and Medical Affairs. "These latest SEIVAL results lend themselves to a hypothesis that intermittent treatment should be further studied to investigate potential biological and behavioral changes that may impact the natural course of seizure clusters."

The first poster presentation introduces an innovative analysis of SEIVAL in patients receiving intermittent rescue treatment with diazepam nasal spray. This exploratory, post hoc analysis demonstrates increased SEIVAL with intermittent treatment across time. Researchers evaluated SEIVAL during 4 90-day periods over 12 months. Mean SEIVAL increased significantly from 12.2 days in Period 1 (P<0.01) to 25.7 days among the consistent cohort of patients with SEIVALs in all 4 periods. No effects of age, treatment duration, change in concomitant medications or quality of life were observed.

The second poster presentation on final effectiveness data from the Phase 3 safety study of diazepam nasal spray shows that second doses, used as a proxy for effectiveness, were administered within 24 hours of the first dose for only 11.5%. of seizure clusters among patients 6-11 years and 12.9% of seizure clusters in patients 12-65 years. These results further support that diazepam nasal spray provides protection for 24 hours. The safety profile in both age groups was similar to and consistent with use of rectal diazepam. Nasal irritation rates were low and transient, and similar to baseline, and no serious treatment-related adverse events occurred, including respiratory depression. The study retention rate was high (~76%) in both age groups.            

Poster Descriptions:

• Examining Change in the Inter–Seizure-Cluster Interval Across Time from a Phase 3, Long- Term Open-Label, Repeat-Dose Safety Study of Diazepam Nasal Spray for the Treatment of Seizure Clusters. (Poster #44)
• Safety and Time to Second Doses in Age Subgroups of Patients With Seizure Clusters Treated With Diazepam Nasal Spray in a Phase 3, Open-Label, Repeat-Dose Safety Study. (Poster #35)

"We continue to explore the robust data set generated by the VALTOCO Phase 3 study in people with uncontrolled epilepsy that experience episodes of frequent seizure activity," said Sunita Misra, M.D., Senior Medical Director. "This data has the potential of evolving the landscape of care for epilepsy patients in the future and we are incredibly encouraged by the exploratory analysis generated thus far."

The posters will be available online to review at the 2^nd North American Epilepsy Congress website beginning May 5 and will be displayed from May 5 through Aug. 8, 2022.

About Neurelis

Neurelis, Inc., is a commercial-stage neuroscience company focused on the development and commercialization of therapeutics for the treatment of epilepsy and orphan neurologic disorders characterized by high unmet medical need.  In 2020, the FDA approved Neurelis' VALTOCO^® (diazepam nasal spray) as an acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from an individual's usual seizure pattern in adult and pediatric patients 6 years of age and older. VALTOCO is a proprietary formulation of diazepam incorporating the science of INTRAVAIL^®. Intravail's transmucosal absorption enhancement technology enables the noninvasive delivery of a broad range of protein, peptide and small-molecule drugs. In its approval of VALTOCO, the U.S. Food and Drug Administration also granted Neurelis Orphan Drug Exclusivity and recognized VALTOCO's intranasal route of administration as a clinically superior contribution to patient care over the previously approved standard-of-care treatment (a rectal gel formulation of diazepam). For more information on VALTOCO, please visit www.valtoco.com. In addition to VALTOCO, Neurelis is developing NRL-2 for intermittent use to control acute panic attacks, NRL-3 as a noninvasive acute therapy to stop seizures that have progressed to status epilepticus, and NRL- 4 as a noninvasive rescue therapy to address the escalation of acute agitation symptoms associated with schizophrenia and bipolar 1 mania in adults. In addition, Neurelis is developing NRL-1049 (previously known as BA-1049), an investigational, pre-clinical stage small molecule Rho kinase (ROCK) inhibitor, for the treatment of cerebral cavernous malformations (CCMS), a rare disorder of the central nervous system (CNS). For more information on Neurelis, please visit www.neurelis.com. For   the    latest    scientific    information    on    VALTOCO, please visit www.neurelismedicalaffairs.com.

Important Safety Information about VALTOCO:

Indication

VALTOCO^® (diazepam nasal spray) is indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from a patient's usual seizure pattern in patients with epilepsy 6 years of age and older.

WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS; ABUSE, MISUSE, AND ADDICTION; and DEPENDENCE AND WITHDRAWAL REACTIONS

• Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.
• The use of benzodiazepines, including VALTOCO, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes. Before prescribing VALTOCO and throughout treatment, assess each patient's risk for abuse, misuse, and addiction.
• The continued use of benzodiazepines may lead to clinically significant physical dependence. The risks of dependence and withdrawal increase with longer treatment duration and higher daily dose. Although VALTOCO is indicated only for intermittent use, if used more frequently than recommended, abrupt discontinuation or rapid dosage reduction of VALTOCO may precipitate acute withdrawal reactions, which can be life-threatening. For patients using VALTOCO more frequently than recommended, to reduce the risk of withdrawal reactions, use a gradual taper to discontinue VALTOCO.

Contraindications: VALTOCO is contraindicated in patients with:

• Hypersensitivity to diazepam
• Acute narrow-angle glaucoma

Central Nervous System (CNS) Depression

Benzodiazepines, including VALTOCO, may produce CNS depression. Caution patients against engaging in hazardous activities requiring mental alertness, such as operating machinery, driving a motor vehicle, or riding a bicycle, until the effects of the drug, such as drowsiness, have subsided, and as their medical condition permits.

The potential for a synergistic CNS-depressant effect when VALTOCO is used with alcohol or other CNS depressants must be considered, and appropriate recommendations made to the patient and/or care partner.

Suicidal Behavior and Ideation

Antiepileptic drugs (AEDs), including VALTOCO, increase the risk of suicidal ideation and behavior. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or unusual changes in mood or behavior.

Glaucoma

Benzodiazepines, including VALTOCO, can increase intraocular pressure in patients with glaucoma. VALTOCO may only be used in patients with open-angle glaucoma only if they are receiving appropriate therapy. VALTOCO is contraindicated in patients with narrow-angle glaucoma.

Risk of Serious Adverse Reactions in Infants due to Benzyl Alcohol Preservative

VALTOCO is not approved for use in neonates or infants. Serious and fatal adverse reactions, including "gasping syndrome," can occur in neonates and low-birth-weight infants treated with benzyl alcohol-preserved drugs, including VALTOCO. The "gasping syndrome" is characterized by central nervous system depression, metabolic acidosis, and gasping respirations. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known.

Adverse Reactions

The most common adverse reactions (at least 4%) were somnolence, headache, and nasal discomfort.

Diazepam, the active ingredient in VALTOCO, is a Schedule IV controlled substance.

To report SUSPECTED ADVERSE REACTIONS, contact Neurelis, Inc. at 1-866-696-3873 or FDA at 1-800-FDA-1088 (www.fda.gov/medwatch).

Please read full Prescribing Information, including Boxed Warning, for additional important safety information.

Contacts:

Neurelis:
Brittany Bradrick, Chief Financial Officer, +1 858 251 2135

Media:
Erich Sandoval, Finn Partners, + 1 917 497 2867

SOURCE Neurelis, Inc.