Impairment of Executive Functions

Magdalena aiming to submit Investigational New Drug (IND) application in 2025 to the FDA for a next-generation psychoactive prescription drug candidate for potential mental health indications such as ADHD and schizophrenia, with 1-2 additional IND applications filed in late 2025/early 2026 SAN FRANCISCO, CA / ACCESS Newswire / February 6, 2025 / Jaguar Health, Inc. (NASDAQ:JAGX) today announced that Dr. Karen Brunke, Jaguar's EVP of Corporate and Business Development and Acting CEO of Magdalena Biosciences, Inc. (Magdalena), the joint venture formed by Jaguar and Filament Health Corp. (OTCQB:FLHLF) (CBOE CA:FH) (FSE:7QS) to develop novel, natural prescription medicines derived from plants for mental health indications, is presenting in person on Monday, February 10, 2025 at 2:30 PM Eastern at the BIO CEO & Investor Conference in New York City. "I very much look forward to providing an overview of Magdalena at this conference and meeting with potential partners and investors at this event," Dr. Brunke said. "We expect Magdalena's lead botanical drug candidate, MB2500, to soon be IND-enabled for one of the following indications: cognitive deficit in schizophrenia or executive dysfunction in attention deficit hyperactivity disorder (ADHD). MB2500 may have the potential to serve as a first-ever treatment for the cognitive deficit that goes untreated in schizophrenia, which is a huge unmet medical need. Schizophrenia is a disease of cognitive deficit, a deficit which appears as much as a decade before onset of psychotic symptoms,1 but no approved drug currently exists to treat cognitive deficit in schizophrenia patients." MB2500 is derived from a well characterized plant that has been in use by local populations for centuries, and has been shown to have both neuroprotective and cognitive enhancing properties, but has never been put through the rigorous clinical testing required for FDA approval. One or two more Magdalena botanical drug candidates for mental health indications are planned to be IND-enabled in late 2025/early 2026. ADHD, a $25 billion global market,2 is a neurodevelopmental disorder characterized by the core symptoms of hyperactivity, inattentiveness, and impulsivity, and there is a growing need for safer ADHD treatments. Schizophrenia is a chronic, disabling mental illness that affects approximately one percent of the U.S. population.3 The global schizophrenia market is projected to grow to $13.41 billion by 2032, according to a market research report by Market Research Future.4 The mission of Magdalena, which is currently approximately 40-percent owned by Jaguar, is to develop novel, safe, efficacious next-generation psychoactive FDA-approved plant-based drugs under FDA Botanical Guidance for mental health indications including schizophrenia, anxiety, depression, and ADHD. Botanical drug candidates have a long history of use by traditional psychiatrists and may have the potential to serve as a new class of plant-based psychoactive drugs which are safe for daily dosing. "Our approach is paradigm-shifting in drug development as we expect to go from plant extract to proof-of-concept (POC) human studies in 12-24 months - a huge time and cost savings which also, based on the history of human medicinal use of the plants, has a higher probability of success," said Dr. Brunke. About Botanicals Drugs Botanicals drugs are defined by the U.S. Food and Drug Administration (FDA) as "products from plant materials, algae, macroscopic fungi, and combinations thereof." Many botanical drugs have a long history of safe use in traditional medicines, which may be documented and reviewed in scientific literature. Existing scientific literature on safety may accelerate the safety review process for a botanical drug, reducing the scope and financial burden for extensive safety studies. The FDA has established guidance on botanical drug development and recognizes the complexity of botanical drugs. Additionally, botanical drugs, by virtue of their complexity, have the added benefit of being difficult to genericize. Hence there are often multiple opportunities for creating ‘trade-secrets,' as well as novel patents around a botanical drug substance, its processing, its formulation, and so forth. The Growing Market for Medicines Derived from Psychoactive Plants According to the World Health Organization, one in four people in the world will be affected by mental or neurological disorders at some point in their lives. Around 450 million people currently suffer from such conditions, placing mental disorders among the leading causes of ill-health and disability worldwide. Among children, ADHD is the most common psychiatric disorder, disrupting learning and social behaviors. Common mental health conditions include depression, PTSD, anxiety, addiction, bipolar disorder (formerly called manic-depressive illness or manic depression), and anorexia nervosa, and expand to include neuro-degenerative diseases such as Parkinson's, Alzheimer's disease, and ALS (amyotrophic lateral sclerosis), among others. Substance use disorders occur when the recurring use of alcohol and/or drugs causes clinically significant impairment, including health problems, disability, and failure to meet major responsibilities at work, home, or school. The Lancet Commission, a group of experts in neuroscience, psychiatry, public health, and related fields, estimates that the cost of mental disorders, currently on the rise in every country, will reach $16 trillion by 2030, including costs associated with lost productivity. About Filament Health (OTCQB:FLHLF) (CBOE CA:FH) (FSE:7QS) Filament Health is a clinical-stage natural psychedelic drug development company. We believe that safe, standardized, naturally-derived psychedelic medicines can improve the lives of many, and our mission is to see them in the hands of everyone who needs them as soon as possible. Filament's platform of proprietary intellectual property enables the discovery, development, and delivery of natural psychedelic medicines. We are paving the way with what we believe to be the first-ever natural psychedelic drug candidates. Learn more at www.filament.health and on Twitter, Instagram and LinkedIn. About the Jaguar Health Family of Companies Jaguar Health, Inc. (Jaguar) is a commercial stage pharmaceuticals company focused on developing novel proprietary prescription medicines sustainably derived from plants from rainforest areas for people and animals with gastrointestinal distress, specifically associated with overactive bowel, which includes symptoms such as chronic debilitating diarrhea, urgency, bowel incontinence, and cramping pain. Jaguar family company Napo Pharmaceuticals (Napo) focuses on developing and commercializing human prescription pharmaceuticals for essential supportive care and management of neglected gastrointestinal symptoms across multiple complicated disease states. Napo's crofelemer is FDA-approved under the brand name Mytesi® for the symptomatic relief of noninfectious diarrhea in adults with HIV/AIDS on antiretroviral therapy. Jaguar family company Napo Therapeutics is an Italian corporation Jaguar established in Milan, Italy in 2021 focused on expanding crofelemer access in Europe and specifically for orphan and/or rare diseases. Jaguar Animal Health is a Jaguar tradename. Magdalena Biosciences, a joint venture formed by Jaguar and Filament Health Corp. that emerged from Jaguar's Entheogen Therapeutics Initiative (ETI), is focused on developing novel prescription medicines derived from plants for mental health indications. For more information about: Jaguar Health, visit https://jaguar.health Napo Pharmaceuticals, visit www.napopharma.com Napo Therapeutics, visit napotherapeutics.com Magdalena Biosciences, visit magdalenabiosciences.com Visit the Make Cancer Less Shitty patient advocacy program on Bluesky, X, Facebook & Instagram Forward-Looking Statements Certain statements in this press release constitute "forward-looking statements." These include statements regarding the expectation that Magdalena management will present at the 2025 BIO CEO & Investor Conference, the expectation that MB2500 will soon be IND-enabled and ready to enter the clinic for the first of two indications, the expectation that MB2500 may have the potential to serve as a first-ever treatment for the cognitive deficit that goes untreated in schizophrenia, the expectation that Magdalena may submit an IND application in 2025 to the FDA for a next-generation psychoactive prescription drug candidate for potential mental health indications such as schizophrenia and ADHD, the expectation that 1-2 more additional Magdalena botanical drug candidates for mental health indications may be IND-enabled in late 2025/early 2026 and submitted as IND applications in late 2025/early 2026, the expectation that MB2500 may have the potential to be an effective treatment for ADHD or the cognitive deficit in schizophrenia, the expectation that botanical drug candidates may have the potential to serve as a new class of plant-based psychoactive drugs which are safe for daily at-home dosing, Magdalena's expectation that Magdalena may be able to go from plant extract to POC human studies within 12-24 months, and the expectation that human studies of Magdalena botanical drug candidates may have a higher probability of success based on the history of human medicinal use of the Magdalena botanical drug candidates. In some cases, you can identify forward-looking statements by terms such as "may," "will," "should," "expect," "plan," "aim," "anticipate," "could," "intend," "target," "project," "contemplate," "believe," "estimate," "predict," "potential" or "continue" or the negative of these terms or other similar expressions. The forward-looking statements in this release are only predictions. Jaguar has based these forward-looking statements largely on its current expectations and projections about future events. These forward-looking statements speak only as of the date of this release and are subject to a number of risks, uncertainties and assumptions, some of which cannot be predicted or quantified and some of which are beyond Jaguar's control. Except as required by applicable law, Jaguar does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. 1 JAMA Psychiatry. 2013;70(10):1107-1112. doi:10.1001/jamapsychiatry.2013.155 2 https://finance.yahoo.com/news/attention-deficit-hyperactivity-disorder-adhd-220000543.html 3 Bromet EJ, Dew MA, Eaton W. Epidemiology of psychosis with special reference to schizophrenia. In: Tsuang MT, Tohen M, Zahner GEP, eds. Textbook in psychiatric epidemiology. New York: John Wiley, 1996:283-300 4 https://www.marketresearchfuture.com/reports/schizophrenia-market-1625 Contact Info: hello@jaguar.health Jaguar-JAGX SOURCE: Jaguar Health, Inc.

Magdalena aiming to submit Investigational New Drug (IND) application in early 2025 to the FDA for a next-generation psychoactive prescription drug candidate for potential mental health indications such as ADHD and schizophrenia, with 1-2 additional IND applications filed in 2025 SAN FRANCISCO, CA / ACCESSWIRE / January 7, 2025 / Jaguar Health, Inc. (NASDAQ:JAGX) today announced that Dr. Karen Brunke, Jaguar\'s EVP of Corporate and Business Development and Acting CEO of Magdalena Biosciences, Inc. (Magdalena), the joint venture formed by Jaguar and Filament Health Corp. (OTCQB:FLHLF)(CBOE CA:FH) (FSE:7QS) to develop novel, natural prescription medicines derived from plants for mental health indications, is presenting in person on Sunday, January 12, 2025 at the Annual Neuroscience Innovation Forum in San Francisco, CA.\"I very much look forward to providing an overview of Magdalena at this conference and meeting with potential partners and investors at this event,\" Dr. Brunke said. \"We expect Magdalena\'s lead botanical drug candidate, MB2500, to soon be IND-enabled and ready to enter the clinic for one of its first indications: executive dysfunction in attention deficit hyperactivity disorder (ADHD) and/or cognitive deficit in schizophrenia. MB2500 may have the potential to serve as a first-ever treatment for the cognitive deficit that goes untreated in schizophrenia, which is a huge unmet medical need. Schizophrenia is a disease of cognitive deficit, a deficit which appears as much as a decade before onset of psychotic symptoms,1 but no approved drug currently exists to treat cognitive deficit in schizophrenia patients.\"\"Our approach is paradigm-shifting in drug development as we expect to go from plant extract to proof-of-concept (POC) human studies in 12-24 months - a huge time and cost savings which also, based on the history of human medicinal use of the plants, has a higher probability of success,\" said Dr. Brunke.MB2500 is derived from a well characterized plant that has been in use by local populations for centuries, has been shown to have both neuroprotective and cognitive enhancing properties, but has never been put through the rigorous clinical testing required for FDA approval. One or two more additional Magdalena botanical drug candidates for mental health indications are planned to be IND-enabled in 2025.ADHD, a $25 billion global market,2 is a neurodevelopmental disorder characterized by the core symptoms of hyperactivity, inattentiveness, and impulsivity, and there is a growing need for safer ADHD treatments. Schizophrenia is a chronic, disabling mental illness that affects approximately one percent of the U.S. population.3 The global schizophrenia market is projected to grow to $13.41 billion by 2032, according to a market research report by Market Research Future.4The mission of Magdalena, which is currently approximately 40-percent owned by Jaguar, is to develop novel, safe, efficacious next-generation psychoactive FDA-approved plant-based drugs under FDA Botanical Guidance for mental health indications including schizophrenia, anxiety, depression, and ADHD. Botanical drug candidates have a long history of use by traditional psychiatrists and may have the potential to serve as a new class of plant-based psychoactive drugs which are safe for daily dosing.About Botanicals DrugsBotanicals drugs are defined by the U.S. Food and Drug Administration (FDA) as \"products from plant materials, algae, macroscopic fungi, and combinations thereof.\" Many botanical drugs have a long history of safe use in traditional medicines, which may be documented and reviewed in scientific literature. Existing scientific literature on safety may accelerate the safety review process for a botanical drug, reducing the scope and financial burden for extensive safety studies. The FDA has established guidance on botanical drug development and recognizes the complexity of botanical drugs. Additionally, botanical drugs, by virtue of their complexity, have the added benefit of being difficult to genericize. Hence there are often multiple opportunities for creating ‘trade-secrets,\' as well as novel patents around a botanical drug substance, its processing, its formulation, and so forth.The Growing Market for Medicines Derived from Psychoactive PlantsAccording to the World Health Organization, one in four people in the world will be affected by mental or neurological disorders at some point in their lives. Around 450 million people currently suffer from such conditions, placing mental disorders among the leading causes of ill-health and disability worldwide. Among children, ADHD is the most common psychiatric disorder, disrupting learning and social behaviors. Common mental health conditions include depression, PTSD, anxiety, addiction, bipolar disorder (formerly called manic-depressive illness or manic depression), and anorexia nervosa, and expand to include neuro-degenerative diseases such as Parkinson\'s, Alzheimer\'s disease, and ALS (amyotrophic lateral sclerosis), among others. Substance use disorders occur when the recurring use of alcohol and/or drugs causes clinically significant impairment, including health problems, disability, and failure to meet major responsibilities at work, home, or school. The Lancet Commission, a group of experts in neuroscience, psychiatry, public health, and related fields, estimates that the cost of mental disorders, currently on the rise in every country, will reach $16 trillion by 2030, including costs associated with lost productivity.About Filament Health (OTCQB:FLHLF) (CBOE CA:FH) (FSE:7QS)Filament Health is a clinical-stage natural psychedelic drug development company. We believe that safe, standardized, naturally-derived psychedelic medicines can improve the lives of many, and our mission is to see them in the hands of everyone who needs them as soon as possible. Filament\'s platform of proprietary intellectual property enables the discovery, development, and delivery of natural psychedelic medicines. We are paving the way with what we believe to be the first-ever natural psychedelic drug candidates.Learn more at www.filament.health and on Twitter, Instagram and LinkedIn.About the Jaguar Health Family of CompaniesJaguar Health, Inc. (Jaguar) is a commercial stage pharmaceuticals company focused on developing novel proprietary prescription medicines sustainably derived from plants from rainforest areas for people and animals with gastrointestinal distress, specifically associated with overactive bowel, which includes symptoms such as chronic debilitating diarrhea, urgency, bowel incontinence, and cramping pain. Jaguar family company Napo Pharmaceuticals (Napo) focuses on developing and commercializing human prescription pharmaceuticals for essential supportive care and management of neglected gastrointestinal symptoms across multiple complicated disease states. Napo\'s crofelemer is FDA-approved under the brand name Mytesi® for the symptomatic relief of noninfectious diarrhea in adults with HIV/AIDS on antiretroviral therapy. Jaguar family company Napo Therapeutics is an Italian corporation Jaguar established in Milan, Italy in 2021 focused on expanding crofelemer access in Europe and specifically for orphan and/or rare diseases. Jaguar Animal Health is a Jaguar tradename. Magdalena Biosciences, a joint venture formed by Jaguar and Filament Health Corp. that emerged from Jaguar\'s Entheogen Therapeutics Initiative (ETI), is focused on developing novel prescription medicines derived from plants for mental health indications.For more information about:Jaguar Health, visit https://jaguar.healthNapo Pharmaceuticals, visit www.napopharma.comNapo Therapeutics, visit napotherapeutics.comMagdalena Biosciences, visit magdalenabiosciences.comVisit the Make Cancer Less Shitty patient advocacy program on Bluesky, X, Facebook & InstagramForward-Looking StatementsCertain statements in this press release constitute \"forward-looking statements.\" These include statements regarding the expectation that Magdalena management will present the 2025 Annual Neuroscience Innovation Forum, the expectation that MB2500 will soon be IND-enabled and ready to enter the clinic for the first of two indications, the expectation that MB2500 may have the potential to serve as a first-ever treatment for the cognitive deficit that goes untreated in schizophrenia, the expectation that Magdalena may submit an IND application in early 2025 to the FDA for a next-generation psychoactive prescription drug candidate for potential mental health indications such as ADHD and schizophrenia, the expectation that 1-2 more additional Magdalena botanical drug candidates for mental health indications may be IND-enabled in 2025 and submitted as IND applications in 2025, the expectation that MB2500 may have the potential to be an effective treatment for ADHD or the cognitive deficit in schizophrenia, the expectation that botanical drug candidates may have the potential to serve as a new class of plant-based psychoactive drugs which are safe for daily at-home dosing, Magdalena\'s expectation that Magdalena may be able to go from plant extract to POC human studies within 12-24 months, and the expectation that human studies of Magdalena botanical drug candidates may have a higher probability of success based on the history of human medicinal use of the Magdalena botanical drug candidates. In some cases, you can identify forward-looking statements by terms such as \"may,\" \"will,\" \"should,\" \"expect,\" \"plan,\" \"aim,\" \"anticipate,\" \"could,\" \"intend,\" \"target,\" \"project,\" \"contemplate,\" \"believe,\" \"estimate,\" \"predict,\" \"potential\" or \"continue\" or the negative of these terms or other similar expressions. The forward-looking statements in this release are only predictions. Jaguar has based these forward-looking statements largely on its current expectations and projections about future events. These forward-looking statements speak only as of the date of this release and are subject to a number of risks, uncertainties and assumptions, some of which cannot be predicted or quantified and some of which are beyond Jaguar\'s control. Except as required by applicable law, Jaguar does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.1 JAMA Psychiatry. 2013;70(10):1107-1112. doi:10.1001/jamapsychiatry.2013.1552 https://finance.yahoo.com/news/attention-deficit-hyperactivity-disorder-adhd-220000543.html3 Bromet EJ, Dew MA, Eaton W. Epidemiology of psychosis with special reference to schizophrenia. In: Tsuang MT, Tohen M, Zahner GEP, eds. Textbook in psychiatric epidemiology. New York: John Wiley, 1996:283-3004https://www.marketresearchfuture.com/reports/schizophrenia-market-1625Source: Jaguar Health, Inc.Contact Info:[email protected]Jaguar-JAGXSOURCE: Jaguar Health, Inc.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that commences subtly. Clinically, it is characterized by comprehensive dementia symptoms including memory impairment, aphasia, apraxia, agnosia, impairment of visuospatial skills, executive function disorder, as well as alterations in personality and behavior. The exact etiology of the disease remains unknown to this day. Acetylcholinesterase (AChE) is an essential enzyme found in the human body that plays a crucial role in the nervous system. It is responsible for breaking down the neurotransmitter acetylcholine (ACh), which is involved in various physiological processes such as muscle contraction, cognition, and memory. AChE ensures the proper functioning of the cholinergic system by rapidly hydrolyzing AChE, preventing its accumulation and maintaining a delicate balance.  Dysfunction or inhibition of AChE can lead to an excess of AChE, resulting in various neurological disorders like Alzheimer's disease and myasthenia gravis. Understanding the role of AChE is vital for developing therapeutic strategies to regulate cholinergic activity and treat associated conditions. AChE inhibitors function by reversibly inhibiting AChE, leading to the accumulation of ACh at synaptic locations, thus extending and enhancing the role of AChE, which in turn improves cognitive functions in Alzheimer's disease (AD) patients. Cholinesterase inhibitors are commonly used to treat patients with mild-to-moderate AD, offering moderate improvements to cognitive function, emotion, behavioral symptoms, and daytime life functions. AChE Competitive LandscapeAccording to the data provided by Patsnap Synapse-Global Drug Intelligence Database: the following figure shows that as of 7 Sep 2023, there are a total of 128 AChE drugs worldwide, from 166 organizations, covering 82 indications, and conducting 1117 clinical trials. 👇Please click on the picture link below for free registration or login directly if you have freemium accounts, you can browse the latest research progress on drugs , indications, organizations, clinical trials, clinical results, and drug patents related to this target. The analysis of the target AChE reveals a competitive landscape with multiple companies actively involved in R&D. AbbVie, Inc., Shanghai Pharmaceuticals Holding Co., Ltd., Pfizer Inc., Zeria Pharmaceutical Co., Ltd., and Eisai Co., Ltd. are among the companies growing fastest in this area.  The approved drugs for the target AChE cover indications such as Myasthenia Gravis, Alzheimer Disease, Poisoning, Glaucoma, and more. Small molecule drugs dominate the drug types progressing rapidly under the target AChE, indicating intense competition.  China, the United States, Japan, and the European Union are the countries/locations developing fastest under the target AChE, with China showing significant progress. Overall, the target AChE presents a promising area for pharmaceutical development, with potential applications in various neurological and gastrointestinal disorders. Key Drug: Donepezil HydrochlorideDonepezil Hydrochloride is a small molecule drug that targets the AChE. It is primarily used in the treatment of nervous system diseases and endocrinology and metabolic diseases. The drug has been approved for the treatment of dementia, Lewy Body Disease, and Alzheimer's Disease. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. The essence of Donepezil Hydrochloride is a highly selective, non-competitive, reversible inhibitor of AChE. Pharmacological studies show that Donepezil Hydrochloride can long-term and effectively inhibit the AChE activity in the central nervous system, increase the ACh levels in the cortical and basal ganglia synapses, activate the central cholinergic system, and significantly improve cognition and memory. Secondly, Donepezil Hydrochloride can protect the stability of neuronal structures, alleviate the toxic side effects of β-amyloid, maintain the normal energy metabolism of central neurons, and play a significant role in maintaining normal brain activity. Finally, Donepezil Hydrochloride has a protective effect on the neuronal bodies in the hippocampus region, has an antioxidant effect, can protect neuronal tissue by reducing the oxidative stress response to neuronal damage, and can regulate the energy metabolism of neuronal bodies to prevent neuronal injury. As Alzheimer's Disease itself is irreversible, it is necessary to regularly evaluate the patient's condition during the intake of Donepezil Hydrochloride. If there are significant declines in memory and cognition, it indicates that the therapeutic effect of Donepezil Hydrochloride is no longer significant. At this point, it may be considered to adjust the dosage or switch to other drugs. Galantamine HydrobromideGalantamine Hydrobromide is a small molecule drug that is primarily used in the treatment of Alzheimer's disease. It targets the AChE, which is responsible for breaking down the neurotransmitter ACh in the brain. By inhibiting AChE, Galantamine Hydrobromide helps to increase the levels of ACh, which is important for memory and cognitive function. The therapeutic area for Galantamine Hydrobromide is nervous system diseases, specifically Alzheimer's disease. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. Galantamine Hydrobromide is a selective, competitive, reversible AChE inhibitor. High in selectivity and competitiveness, it competes with ACh in the synaptic gap for binding with AChE, thus blocking this enzyme from breaking down ACh. This implies that Galantamine Hydrobromide can generate maximum activity in areas with post-synaptic cholinergic deficiency. As the therapeutic effects mainly occur post-synaptically, this characteristic allows Galantamine Hydrobromide to achieve maximal clinical effectiveness. Galantamine Hydrobromide has received approval for use in both the global market and China. The drug was first approved in the United States in February 2001, making it one of the early treatments available for Alzheimer's disease. Since then, it has been approved in several other countries as well. The approval of Galantamine Hydrobromide in multiple countries highlights its efficacy and safety profile in the treatment of Alzheimer's disease. It has undergone rigorous clinical trials to demonstrate its benefits and potential side effects.  As a small molecule drug, Galantamine Hydrobromide is likely to be available in oral dosage forms, such as tablets or capsules. This allows for convenient administration and patient compliance. In summary, Galantamine Hydrobromide is a small molecule drug that targets AChE and is used in the treatment of Alzheimer's disease. It has received approval in both the global market and China, with its first approval in the United States in 2001. The drug's approval highlights its efficacy and safety in treating Alzheimer's disease, a significant therapeutic area in the field of biomedicine.