NEURELIS ANNOUNCES FILING OF ITS INVESTIGATIONAL NEW DRUG APPLICATION FOR NRL-1049, A RHO KINASE (ROCK) INHIBITOR WITH POTENTIAL TO TREAT CEREBRAL CAVERNOUS MALFORMATIONS

• Pre-clinical data recently presented at Society for Neuroscience's annual meeting demonstrates NRL-1049 potential safety, Neurelis to advance further studies

SAN DIEGO, Jan. 9, 2023 /PRNewswire/ -- Neurelis, Inc., announced the successful filing of its investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for NRL-1049, a Rho kinase (ROCK) inhibitor with a potential treatment for people living with cerebral cavernous malformations (CCM), a disease characterized by abnormally enlarged capillary cavities in the brain and spinal cord.

"This is a significant milestone for Neurelis and represents an opportunity to further explore the clinical utility of NRL-1049 for the treatment of cerebral cavernous malformations," said Adrian L. Rabinowicz, M.D., Neurelis SVP Clinical Development and Medical Affairs. "Following favorable preclinical study results, we are excited to advance our mission to introduce new treatment options for patients with critical unmet medical needs."

Following the IND filing, the Company plans to initiate a clinical study evaluating the safety of NRL-1049 in early 2023.

An analysis of NRL-1049 preclinical data was presented at the Neuroscience 2022 Conference (San Diego, CA, November 12- 16, 2022), hosted by the Society for Neuroscience (SfN). The analysis showed that in two different animal models of brain injury, NRL-1049 protected the brain, possibly through maintaining the integrity of the blood-brain barrier through a decrease in ROCK2 activation. This protection was associated with lower rates of brain edema in both animal models. A lower seizure rate in the cold injury animals and decreased intracerebral hemorrhage in the model of stroke were also observed.

"We are excited that the preclinical studies have shown that NRL-1049 is safe and efficacious in animal models," said Enrique Carrazana, M.D., Neurelis Chief Medical Officer. "Based on the significance of these data, Neurelis is developing further studies in humans to assess the safety of NRL-1049 in the treatment of chronic and acute conditions that affect the functioning of the blood-brain barrier. If successfully developed and approved, NRL-1049 has the potential to provide relief to people suffering from CCMs."

CCMs are a disease characterized by abnormally enlarged capillary cavities, most commonly found in the cerebral cortex, brainstem, and spinal cord. CCMs can present as a single lesion or as multiple lesions. Depending on lesion size and location, CCMs can be "clinically silent" or can present with clinical symptoms ranging from headaches to focal neurological deficits, seizures, and cerebral hemorrhage. People afflicted with CCMs have limited treatment options, which include management of seizures through anti-epileptic drugs and surgical intervention to remove lesions (e.g., microsurgical resection, stereotactic radiosurgery). There are no FDA-approved therapeutic treatments for CCMs. Most cavernous malformations are conservatively managed by observing for changes in appearance, recent hemorrhages, or other clinical symptoms.

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 http://www.valtoco.com/. In addition to VALTOCO, Neurelis is developing 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, phase 1, 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 http://www.neurelis.com/. For the latest scientific information on VALTOCO, please visit http://www.neurelismedicalaffairs.com/.

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

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.

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.

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.

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.

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

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

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

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

SOURCE Neurelis, Inc.