BioAxone BioSciences, Inc.

SAN DIEGO, CA, USA I March 24, 2023 I Neurelis, Inc., announced the first two cohorts dosed in the investigational clinical trial of NRL-1049, a Rho kinase (ROCK) inhibitor, 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 first-in-human study designed to establish safety, tolerability, and pharmacokinetic parameters of NRL-1049. "We are excited to initiate this study because it will build upon the preclinical activity and tolerability observed in preclinical studies. People afflicted with CCMs have limited treatment options, which include management of seizures through anti-seizure medications and in limited selected cases surgical intervention to remove lesions," said Founder and CEO of Neurelis, Craig Chambliss. "If successful, NRL-1049 has the potential to be the first FDA approved treatment for CCMs." An analysis of NRL-1049 preclinical data showed that transgenic mice showing the mutations for familial CCMs treated with NRL-1049 showed a significant dose-dependent reduction in lesion volume and a reduction in hemorrhage (iron deposition) near lesions at all doses after treatment compared with placebo. NRL-1049 will be evaluated in a randomized, dose-escalation, double-blind, placebo-controlled single ascending dose study to establish safety, tolerability, and pharmacokinetic parameters in healthy volunteers. The primary objectives of the study are to determine the maximum tolerated dose (MTD) of a single oral dose of NRL-1049 and collect data on clinical safety and tolerability. "The NRL-1049 Phase 1 study was built on strong preclinical data, both providing greater insight into its potential, which helped inform our decision to initiate this clinical program," said Chief Scientific Officer, Stuart Madden, PHD, CCHEM, FRSC. "We are excited about what NRL-1049 could mean for patients and appreciate the contributions of the trial volunteers and investigators." About NRL-1049 In June 2021, Neurelis licensed NRL-1049 from BioAxone BioSciences, Inc., which is an investigational pre-clinical stage small molecule, Rho kinase (ROCK) inhibitor designed to potentially reduce the accumulation of new lesions, as well as alleviate neurological symptoms associated with CCMs. Earlier this year, the investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) was accepted for NRL-1049. Cerebral Cavernous Malformations 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-seizure medications 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. 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 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 I 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 https://www.neurelismedicalaffairs.com/.

First in human study will evaluate safety, tolerability, and pharmacokinetic parameters of NRL-1049, a Rho kinase (ROCK) inhibitor SAN DIEGO, Calif., March 24, 2023 /PRNewswire/ -- Neurelis, Inc., announced the first two cohorts dosed in the investigational clinical trial of NRL-1049, a Rho kinase (ROCK) inhibitor, 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 first-in-human study designed to establish safety, tolerability, and pharmacokinetic parameters of NRL-1049. "We are excited to initiate this study because it will build upon the preclinical activity and tolerability observed in preclinical studies. People afflicted with CCMs have limited treatment options, which include management of seizures through anti-seizure medications and in limited selected cases surgical intervention to remove lesions," said Founder and CEO of Neurelis, Craig Chambliss. "If successful, NRL-1049 has the potential to be the first FDA approved treatment for CCMs." An analysis of NRL-1049 preclinical data showed that transgenic mice showing the mutations for familial CCMs treated with NRL-1049 showed a significant dose-dependent reduction in lesion volume and a reduction in hemorrhage (iron deposition) near lesions at all doses after treatment compared with placebo. NRL-1049 will be evaluated in a randomized, dose-escalation, double-blind, placebo-controlled single ascending dose study to establish safety, tolerability, and pharmacokinetic parameters in healthy volunteers. The primary objectives of the study are to determine the maximum tolerated dose (MTD) of a single oral dose of NRL-1049 and collect data on clinical safety and tolerability. "The NRL-1049 Phase 1 study was built on strong preclinical data, both providing greater insight into its potential, which helped inform our decision to initiate this clinical program," said Chief Scientific Officer, Stuart Madden, PHD, CCHEM, FRSC. "We are excited about what NRL-1049 could mean for patients and appreciate the contributions of the trial volunteers and investigators." About NRL-1049 In June 2021, Neurelis licensed NRL-1049 from BioAxone BioSciences, Inc., which is an investigational pre-clinical stage small molecule, Rho kinase (ROCK) inhibitor designed to potentially reduce the accumulation of new lesions, as well as alleviate neurological symptoms associated with CCMs. Earlier this year, the investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) was accepted for NRL-1049. Cerebral Cavernous Malformations 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-seizure medications 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. 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 . 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 I 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 . For the latest scientific information on VALTOCO, please visit . Important Safety Information about VALTOCO: Indication 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. 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 be used in patients with open-angle glaucoma only if they are receiving appropriate therapy. VALTOCO is contraindicated in patients with narrow-angle glaucoma. Neonatal Sedation and Withdrawal Syndrome Use of VALTOCO late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in the neonate. Monitor neonates exposed to VALTOCO during pregnancy or labor for signs of sedation and monitor neonates exposed to VALTOCO during pregnancy for signs of withdrawal; manage these neonates accordingly. 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 (). Please read full Prescribing Information , including Boxed Warning. Contacts: Neurelis: Brittany Bradrick, Chief Operating Officer and Chief Financial Officer, +1 858 251 2135 Media: Glenn Silver, FINN Partners, +1 646 871 8485 SOURCE Neurelis, Inc.

Seeking Global Licensing Partner for Phase 3 Clinical Development and Commercialization; FDA has granted Orphan Drug Status and Fast Track designation BOSTON--(BUSINESS WIRE)-- BioAxone BioSciences, Inc., a clinical stage biotechnology company committed to discovering and developing drugs for neurological conditions, today announced that a new patent has been issued for BA-210, a Phase 3-ready pro-regenerative drug candidate for the treatment of spinal cord injury. The new U.S. patent 11,324,802 covers pharmaceutical compositions of BA-210. “There is an urgent unmet need for new medicines for patients with acute spinal cord injuries,” said Lisa McKerracher, PhD, CEO, BioAxone BioSciences. “When central nervous system trauma occurs, neuronal Rho is ‘hyperactivated’ and that halts axon regeneration.” Dr. McKerracher continued, “Rho is the signaling molecule that acts as the ‘mastermind switch’ that regulates the growth and regeneration of injured axons. By inactivating Rho, BA-210 is designed to stimulate the regeneration of cut axons.” Rho as a target to treat spinal cord injury has been validated by multiple laboratories. After a spinal cord injury, the enzyme Rho regulates events that culminate in collapse of the neuronal growth cone, failure of axonal regeneration, and, ultimately, failure of motor and functional recovery. BA-210 is a first-in-class, topically applied, biologic Rho inhibitor. BioAxone BioSciences developed BA-210 to inactivate Rho and has brought the compound forward to clinical testing. BA-210 has both orphan drug status and Fast Track designation from the FDA. BioAxone Biosciences seeks a global licensing partner for clinical development and commercialization of the drug candidate which has a demonstrated safety pro reported clinical data from completed Phase 1b and Phase 2b clinical trials. The newly issued patent extends the commercial opportunity for BA-210. BioAxone has previously partnered a proprietary portfolio of ROCK2 selective Rho kinase inhibitors. The lead compound is an oral kinase inhibitor for treatment of cerebral cavernous malformation (CCM) and other neurovascular disorders. The NIH Small Business Innovation Research program supported proof of concept studies. About BioAxone BioSciences, Inc. Based in Boston, BioAxone BioSciences is a clinical stage, neuroscience biotechnology company which applies its deep understanding of axon regeneration and neuronal signaling pathways to discover and develop new medicines 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 BA-210, for the treatment of acute spinal cord injury. The company is seeking a global licensing partner for BA-210 to take on clinical development and commercialization. A second drug development program for treatment of spinal cord injury is focused on the intrinsic barriers to regeneration brought on by neuronal aging. This compound is in preclinical testing in collaboration with the Tanenbaum Open Science Institute of McGill University. For more information, visit .