● Adds to Neurelis’s growing pipeline of innovative neuroscience programs
● There are no currently FDA-approved treatments for Cerebral Cavernous Malformations (CCMs)
● Neurelis intends to submit an Investigational New Drug (IND) application with the FDA on BioAxone’s lead compound, BA-1049, in 2022
SAN DIEGO, CA — June 21, 2021 — Neurelis, Inc., announced today that it has acquired from BioAxone Biosciences, Inc. a portfolio of novel ROCK-2 Inhibitors that target cerebral cavernous malformations (CCMs), a rare disorder of the central nervous system (CNS) that currently have no pharmacologic treatments available.
Craig C. Chambliss, President and Chief Executive Officer of Neurelis, states, “We are very excited to continue the development of these novel compounds and work towards progressing BA-1049, BioAxone’s lead compound, into the clinic. We understand the high unmet need faced by patients diagnosed with cerebral cavernous malformations and the overlap with our focus in epilepsy, given the prevalence of seizure activity resulting from CCMs. Adding BA-1049 to our pipeline highlights our commitment to developing new therapies for patients and strengthens our position as an innovative neuroscience company.”
CCMs are an orphan and rare disease characterized by abnormally enlarged capillary cavities most commonly found in the cerebral cortex, brainstem and spinal cord. CCMs can present as a single or as multiple lesions and, depending on size and location, can be “clinically silent” or can present with clinical symptoms ranging from headaches to focal neurological deﬁcits, seizures and cerebral hemorrhage. CCMs can arise sporadically or may be inherited (familial). Familial CCMs, which arise from autosomal dominant mutations in the CCM1, CCM2 and/or CCM3 genes, account for at least 20% of all cases. Mutations in the CCM1-CCM3 genes all cause hyperactivation of the Rho/ROCK signaling pathway in brain vascular endothelial cells (ROCK). Hyperactivation of ROCK then contributes to the loss of endothelial integrity, leading to capillary malformation and eventually to the potential for lesions. The lifetime risk of seizures and hemorrhage for patients affected with CCMs is 40%-70% and 41%, respectively. The prevalence of CCMs in the general population is 0.2%-0.5% and they account for a large proportion (8%-15%) of all brain and spinal vascular malformations. Children represent approximately 25% of all diagnosed individuals.
Patients afflicted with CCMs have limited treatment options, which include management of seizures through antiepileptic drugs and surgical intervention to remove lesions (e.g., microsurgical resection, stereotactic radiosurgery). There are currently no approved treatments for CCMs, and most cavernous malformations are conservatively managed by observing for change in appearance, recent hemorrhage, or clinical symptoms.
Enrique Carrazana, M.D., Chief Medical Officer for Neurelis, states, “BioAxone’s lead product, BA-1049, offers an opportunity to treat CCMs by stabilizing lesions, but also by possibly preventing new lesions from emerging. We are excited by the prospects of this mechanism and look forward to the clinical development of BA-1049 to determine its safety and efficacy.” Neurelis intends to submit an Investigational New Drug Application for BA-1049 in 2022.
Research for preclinical development of BA-1049 was supported by National Institutes of Health (NIH) Small Business Innovation Research grants.
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’s 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. For more information on Neurelis, please visit www.neurelis.com.
About BioAxone BioSciences, Inc.
BioAxone BioSciences is a biotechnology company based in Boston, committed to applying its deep understanding of axon regeneration and neuronal signaling pathways to transform the lives of patients afflicted with neurotrauma or neurovascular disorders. Leveraging 20 years of pioneering research in axon regeneration and diseases involving Rho/ROCK signaling, BioAxone’s lead drug candidate is an orally available ROCK2 inhibitor restoring endothelial cell barriers in cavernous angioma (CA) and stroke. The Company’s pipeline also includes programs to develop drug candidates for the treatment of spinal cord injury. For more information, visit www.bioaxonebio.com.
Important Safety Information about VALTOCO:
VALTOCO® (diazepam nasal spray) is indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, 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.
IMPORTANT SAFETY INFORMATION
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.
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.
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.