5-HT1B receptor

Novel compounds protected under Enveric’s intellectual property portfolio provide potential licensing opportunities and non-dilutive revenue streams. CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Enveric Biosciences (NASDAQ: ENVB) (“Enveric” or the “Company”), a biotechnology company dedicated to the development of novel neuroplastogenic small-molecule therapeutics for the treatment of depression, anxiety, and addiction disorders, today announced the discovery of multiple, promising novel compounds sourced using the company’s Psybrary™ platform and proprietary computational chemistry and artificial intelligence (AI) drug-discovery system (PsyAI™). The novel compounds span seven distinct molecule classes totaling at least 57 unique product opportunities, all of which are protected by Enveric’s expansive intellectual property portfolio and represent potential out-licensing opportunities and non-dilutive revenue streams for the Company. Together, the novel and distinct molecule classes broaden and deepen Enveric’s library of assets targeting difficult-to-address mental health disorders, adding to its lead candidate EB-003, a first-in-class neuroplastogen designed to eliminate hallucinations, and EB-002, formerly EB-373, a next generation synthetic prodrug of the active metabolite, psilocin. “Our ability to identify EB-003 and EB-002 as our lead drug candidates was the result of an extensive process in which our research team analyzed more than one thousand compounds spanning numerous classes of molecules, utilizing our proprietary PsyAI and Psybrary platforms,” said Joseph Tucker, Ph.D., Director and CEO of Enveric. “As a result, Enveric now possesses what we believe to be one of the most diverse portfolios of potential drug molecules for the treatment of key, underserved mental health and neurological disorders. Our dedicated approach to protecting our discoveries should enable us to generate significant near- and long-term value for our shareholders via potential partnering and/or licensing agreements.” The novel compounds span seven diverse molecule classes and subclasses, including: Novel Serotonin-Norepinephrine-Dopamine Reuptake Inhibitors (SNDRI) Also known as triple reuptake inhibitors (TRIs), SNDRIs are an emerging class of medications designed to treat severe depression and anxiety disorders. Enveric SNDRI compounds show strong binding to serotonin transporter (SERT), norepinephrine transporter (NET) and dopamine transporter (DAT). Enveric SNDRI compounds also demonstrate distinct additional serotonin receptor binding profiles that bear similarities to those of the antidepressant Nefazodone and the anxiolytic Buspirone. Non-selective Serotonin Reuptake Inhibitor (NSRI) Enveric NSRI compounds show strong binding to SERT, as well as to the 5-HT1A receptor, known to be a therapeutically valuable target. Certain of Enveric’s NSRIs demonstrate additional binding to various serotonin and dopamine family receptors, with binding profiles similar to the antidepressant Vortioxetine and the atypical antipsychotic Aripiprazole. Novel MDMA Derivatives (EMD) Series Twenty novel MDMA derivatives are separated into three subgroups: Strong 5-HT2A receptor binding, Weak 5-HT2A binding, and No 5-HT2A receptor binding. Current literature indicates agonism of the 5-HT2A receptor is linked to hallucination in humans and also to the induction of neuroplasticity. Each subgroup of Enveric’s novel MDMA derivatives demonstrates unique and expanded receptor binding activity targeting adrenergic and/or dopaminergic receptors as well as epinephrine/norepinephrine family receptors. Some of the resulting receptor binding profiles are similar to the anxiolytic Buspirone, the antiepileptic Fenfluramine, the ADHD drug Guanfacine, and the atypical antipsychotic Aripiprazole. Bifunctional Psilocin Prodrugs (BPP) BPPs are readily absorbed, detectable in plasma, and converted to therapeutically relevant levels of plasma psilocin, with demonstrated lower Head Twitch Response (HTR) relative to psilocybin in mice; HTR is reported in the literature to be a predictive indicator for hallucination in humans. Each BPP parent prodrug demonstrates its own unique binding pro serotonin 5-HT1A receptor, 5-HT1B receptor and SERT, with similarities to anxiolytics Buspirone, antidepressant/anxiolytic Flesinoxan, and the antidepressant Paroxetine. Novel Psilocin Prodrug (NPP) Series NPPs are designed to be metabolized to release therapeutic levels of systemic psilocin at varying rates, providing treatment regimen optionality. Included in this series are four compounds that can be converted upon direct intravenous injection to psilocin: potentially bypassing the need for first-pass metabolism, making them amenable to non-oral forms of administration (e.g. intranasal, sublingual, buccal). Melatonin-Receptor Agonist (MRA) Series Melatonin, a natural indolamine, is essential for regulating circadian rhythm in mammals and is often used in to treat a variety of sleep disorders. Enveric MRA compounds demonstrate strong binding to the MT1 Melatonin receptor with some being highly selective for MT1 while others demonstrate expanded target binding profiles similar to the antidepressants Agomelatine, Vortioxetine, Imipramine, and Trazodone. Neuroplastogenic Antidepressant (NAD-01) Designed to induce neuroplasticity and promote long-term therapeutic benefit in patients suffering from severe depressive mood disorders. Demonstrates neuroplastogenic activity comparable to known 5-HT2A receptor agonist N,N-Dimethyltryptamine (DMT). Demonstrates weak 5-HT2A receptor binding affinity and activation. Produces lower Head Twitch Response relative to psilocin and DMT, while promoting recovery of sucrose preference (SP) in stressed mice - an accepted model for evaluation of antidepressant activity. For more information about Enveric’s novel preclinical compounds spanning multiple, distinct classes of molecules, please visit: . About Enveric Biosciences Enveric Biosciences (NASDAQ: ENVB) is a biotechnology company dedicated to the development of novel neuroplastogenic small-molecule therapeutics for the treatment of depression, anxiety, and addiction disorders. Leveraging its unique discovery and development platform, Psybrary™, Enveric has created a robust intellectual property portfolio of New Chemical Entities for specific mental health indications. Enveric’s lead program, EB-003, is a first-in-class approach to the treatment of difficult-to-address mental health disorders designed to promote neuroplasticity without inducing hallucinations in the patient. Enveric is also developing EB-002, formerly EB-373, a next generation synthetic prodrug of the active metabolite, psilocin, being studied as a treatment of psychiatric disorders. Enveric is headquartered in Naples, FL with offices in Cambridge, MA and Calgary, AB Canada. For more information, please visit . Forward-Looking Statements This press release contains forward-looking statements and forward-looking information within the meaning of applicable securities laws. These statements relate to future events or future performance. All statements other than statements of historical fact may be forward-looking statements or information. Generally, forward-looking statements and information may be identified by the use of forward-looking terminology such as “plans,” “expects” or “does not expect,” “proposed,” “is expected,” “budgets,” “scheduled,” “estimates,” “forecasts,” “intends,” “anticipates” or “does not anticipate,” or “believes,” or variations of such words and phrases, or by the use of words or phrases which state that certain actions, events or results may, could, should, would, or might occur or be achieved. Forward-looking statements may include historical statements and statements regarding beliefs, plans, expectations, or intentions regarding the future and are based on the beliefs of management as well as assumptions made by and information currently available to management. Actual results could differ materially from those contemplated by the forward-looking statements as a result of certain factors, including, but not limited to, the ability of Enveric to: carry out successful clinical programs in Australia; achieve the value creation contemplated by technical developments; avoid delays in planned clinical trials; establish that potential products are efficacious or safe in preclinical or clinical trials; establish or maintain collaborations for the development of therapeutic candidates; obtain appropriate or necessary governmental approvals to market potential products; obtain future funding for product development and working capital on commercially reasonable terms; scale-up manufacture of product candidates; respond to changes in the size and nature of competitors; hire and retain key executives and scientists; secure and enforce legal rights related to Enveric’s products, including patent protection; identify and pursue alternative routes to capture value from its research and development pipeline assets; continue as a going concern; and manage its future growth effectively. A discussion of these and other factors, including risks and uncertainties with respect to Enveric, is set forth in Enveric’s filings with the Securities and Exchange Commission, including Enveric’s Annual Report on Form 10-K and its Quarterly Reports on Form 10-Q. Enveric disclaims any intention or obligation to revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

VALBY, Denmark, Oct. 18, 2022 /PRNewswire/ -- H. Lundbeck A/S (Lundbeck) announced positive data showing Trintellix/Brintellix® (vortioxetine) significantly reduced depressive symptoms and improved cognitive performance in people living with Major Depressive Disorder (MDD) and co-morbid dementia. This data was presented at the 35th European College of Neuropsychopharmacology (ECNP) Congress, October 15-18, 2022, in Vienna, Austria. "MDD is a risk factor for developing dementia, and dementia is an aggravating factor for MDD. Both are clinical conditions with high unmet need and commonly occur as co-morbidities1," says Johan Luthman, Executive Vice President, Research and Development at Lundbeck. "We are pleased to share data which reinforces the safety and efficacy of vortioxetine on depressive symptoms and sheds new light on its potential to improve cognitive performance in adults aged 55 and older living with MDD and co-morbid early dementia." MEMORY study results met the primary endpoint, showing significant improvement in symptoms of depression as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS). MEMORY study results demonstrated a clinically meaningful2 reduction of 12.4 points from the baseline to week 12 (p<0.0001). Secondary endpoints in the study measuring cognitive performance were also met, as shown by significant and clinically relevant improvements in the Digit Symbol Substitution Test (DSST); a measure of attention, working memory, learning ability, and processing speed, and the Rey Auditory Verbal Learning Test (RAVLT); a measure verbal memory. The specific improvement as measured from baseline in standardized effect sizes were: Digit Symbol Substitution Test (DSST): Week 4=0.52 (p<0.0001) and Week 12=0.65, p<0.0001 Rey Auditory Verbal Learning Test (RAVLT) immediate recall: Week 4=0.26, p=0.0361; Week 12=0.28, p=0.0176 RAVLT delayed recall: Week 4=0.32, p=0.0047; Week 12=0.33, p=0.0062 Significant improvement in patients' health-related quality of life as measured by the Bath Assessment of Subjective Quality of Life in Dementia (BASQID) was also observed from week four (change from baseline in total score = 4.4; p<0.0001) and increasing in effect until week 12 (change from baseline = 10.2; p<0.0001). Safety and tolerability data reported in the study were consistent with data from the pivotal development program of vortioxetine, confirming the tolerability profile of the compound. Depression and dementia commonly co-occur. Depression occurs in approximately 20–30% of patients with Alzheimer's disease and is even more prevalent in patients with vascular dementia and dementia with Lewy bodies1. Patients with depressive symptoms have a 1.2–2.4x higher risk of developing dementia than those without depressive symptoms2-6. The presence of depressive symptoms in dementia worsens patient outcomes, resulting in increased mortality rates,7 greater functional impairment,8 worse health-related quality of life,8 decreased cognitive function9 and increased Behavioural and Psychological Symptoms of Dementia10. More information about the study and Lundbeck at ECNP 2022 can be viewed here. About the MEMORY study The study was a 12-week interventional, open-label effectiveness study of flexible doses of vortioxetine (5-20 mg) with a primary objective to investigate the effect on depressive symptoms in patients with MDD comorbid with early dementia. The study was conducted at 24 sites in a psychiatric outpatient setting across five countries: Estonia, France, Italy, Poland, and Spain. In total, 83 patients were enrolled in the MEMORY study and had a primary diagnosis of recurrent MDD (with onset before the age of 55) and comorbid diagnosis of early dementia (with onset at least 6 months before screening and after already being diagnosed with MDD). Patients were treated open-label with 5 mg vortioxetine once daily for the first week, and then up-titrated to 10 mg/day at week one. Thereafter the dose could be adjusted to according to the patient's response. From week eight till week 12, 43% of the patients were treated with 10 mg and 51% with 20 mg. About vortioxetine The mechanism of the antidepressant effect of vortioxetine is not fully understood. It is an inhibitor of serotonin (5-HT) reuptake and that is thought to be a mechanism of its action. It is also an agonist at 5-HT1A receptors, a partial agonist at 5-HT1B receptors and an antagonist at 5-HT3, 5-HT1D and 5-HT7 receptors. The contribution of each of these activities to vortioxetine's antidepressant effect has not been established. Vortioxetine is considered to be the first and only compound with this combination of pharmacodynamic activity. The clinical relevance of this is not fully understood. Vortioxetine was discovered by Lundbeck researchers in Copenhagen, Denmark. Depending on the market, vortioxetine is known as Trintellix® or Brintellix®. About Lundbeck Lundbeck is a global pharmaceutical company specialized in brain diseases. For more than 70 years, we have been at the forefront of neuroscience research. We are tirelessly dedicated to restoring brain health, so every person can be their best. We are committed to fighting stigma and discrimination against people living with brain diseases and advocating for broader social acceptance of people with brain health conditions. Our research programs tackle some of the most complex challenges in neuroscience, and our pipeline is focused on bringing forward transformative treatments for brain diseases for which there are few, if any therapeutic options. For additional information, we encourage you to visit our corporate site and connect with us on Twitter at @Lundbeck and via LinkedIn. Citations Byers AL, Kristine Y. Nat Rev Neurol. 2012; 7: 323–31 Cohen J (1988) Statistical power analysis for the behavioral sciences, Second Edition. Hillsdale, NJ: Lawrence Erlbaum Associates, Publishers. Enache D et al. Curr Opin Psychiatry 2011;24:461-72. Alzheimer's Disease International. World Alzheimer Report 2014. Available at: . Accessed September 2022. Barnes DE et al. Arch Gen Psychiatry 2012;69:493-8. Santabárbara J et al. Actas Esp Psiquiatr 2020;48:169-80. Almeida OP et al. Transl Psychiatry 2017;7:e1117. Holmquist S et al. PLoS Med 2020;17:e1003016. Lavretsky H et al. Am J Psychiatry 2010;167:589-97. Feng L et al. Int Psychogeriatr 2010;22:246-53. Prado-Jean A et al. Int J Geriatr Psychiatry 2010;25:1065-72 Goodarzi Z et al. BMC Neurol 2016;16:244. CONTACT: H. Lundbeck A/S Ottiliavej 9, 2500 Valby, Denmark +45 3630 1311 [email protected] The following files are available for download: SOURCE H. Lundbeck A/S

VIENNA, Austria, Aug. 01, 2022 (GLOBE NEWSWIRE) -- The AOP Health Group (AOP Health) is a European pioneer for integrated therapies for rare diseases and in critical care headquartered in Vienna, Austria. The company focuses on research, development and global sales of innovative treatment solutions and specializes in therapies for rare diseases and intensive care. In early July, AOP Health signed an agreement with Leukos Biotech, a spin-off company founded by the Barcelona-based Josep Carreras Leukaemia Research Institute. The agreement signed by AOP Health covers the option for developments of the newly discovered chemical substance within any treatable indication, not limited to oncological or rare diseases. Agreement sets basis for new areas of therapy At first, AOP Health will focus on the development of treatment options for Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS). Both are special disease types of leukemia that often start in the bone marrow. Agnes Kohl, Chief Business Officer of AOP Orphan Pharmaceuticals GmbH, Member of the AOP Health Group explains: “Based on positive data, our plan is to expand the development for further orphan indications even outside of AML and MDS at a later stage. With this agreement, we may be able to broaden the portfolio within our therapeutic areas offering even more treatment options for patients.” Development in cooperation with Leukos As AOP Health focuses on rare, hemato-oncological cancers and has many years of experience in the development and commercialization of hemato-oncological treatments, the company will drive the further development of the substance in cooperation with Leukos based on a new mode of action. This could potentially turn into a milestone in the treatment of many blood cancer and other cancer patients. Luis Ruiz-Avila, Chief Executive Officer of Leukos Biotech: “We focus on developing new treatments for a wide variety of tumors. We were born to transform excellent science from the Josep Carreras Leukaemia Research Institute into valuable products for cancer patients in need, and this agreement is a very significant step in that direction. We are convinced that AOP Health is the right partner to turn this promising, novel mechanism of action into a clinical reality for the benefit of patients in a wide variety of unmet medical needs”. About AOP Health The AOP Health Group incorporates several companies including AOP Orphan Pharmaceuticals GmbH with its seat in Vienna, Austria (“AOP Health”). The AOP Health Group is the European pioneer for integrated therapies for rare diseases and in critical care. Over the past 25 years, the Group has become an established provider of integrated therapy solutions operating from its headquarters in Vienna, its subsidiaries and representative offices throughout Europe and the Middle East, as well as through partners worldwide. This development has been made possible by a continually high level of investment in research and development on the one hand and a highly consistent and pragmatic orientation towards the needs of all its stakeholders on the other – especially the patients and their families as well as also the healthcare professionals treating them. About Leukos Leukos Biotech, SL (Leukos) is a spin-off company from the Josep Carreras Leukaemia Research Institute incorporated in Barcelona in 2015. The company is developing new treatments and diagnostic tools for a wide variety of tumors targeting the serotonin receptor HTR1B, which antitumoral potential was first described and patented by Leukos’ founder Dr. Ruth Risueño in her laboratory at the Josep Carreras Research Institute. Leukos’ main financial support is from private and institutional investors. The main shareholders are Inveready, CDTI Innvierte and the Josep Carreras Foundation. Besides investors’ support, Leukos has received non-dilutive grants and loans from the Catalan Government, the Spanish Government and the European Union in various programs. About the Josep Carreras Foundation The Josep Carreras Leukaemia Foundation was established in 1988 with the intention of contributing to finding a definitive cure for this disease. Its efforts are concentrated on four basic areas: administering the Spanish Bone Marrow Donor Registry (REDMO), scientific research, carried out by the Josep Carreras Leukaemia Research Institute, patient guidance through an online patient consultation channel, and reception apartments for patients who need to undergo treatment and have to spend a long time far from home. About the Josep Carreras Leukaemia Research Institute The Josep Carreras Leukaemia Research Institute, a public centre pertaining to the Generalitat de Catalunya's CERCA network, was established in 2010 with the aim of furthering biomedical research and personalised medicine in the field of leukaemia and other onco-hematological diseases. It is the first research centre in Europe exclusively focussed on leukaemia and malignant blood diseases, and one of the very few in the world. The Josep Carreras Institutes has three coordinated but independent scientific campuses: University of Barcelona Hospital Clínic Campus, The Catalan Institute of Oncology/Germans Trias i Pujol Campus, and the Sant Pau - Autonomous University of Barcelona (UAB) Campus About Inveready Inveready is a leading alternative asset manager in Spain - investing in early-stage VC, growth VC, venture debt, strategic equity in listed companies, infrastructure and private equity - providing financing solutions to companies throughout their life-cycle. Founded in 2008, Inveready counts on 200 active companies, and more than €1bn of assets under management. Inveready has been investing in companies in the Life Sciences sector since 2008. Notable investments in this vertical are Atrys Health (listed on the Spanish market), EDESA Biotech (listed on Nasdaq), AVX Pharma (sold to Aerie Biotech) and PaloBiofarma (licensing agreement with Novartis). Inveready is headquartered in San Sebastian, and has other offices in Barcelona and Madrid. It has been recognized on multiple occasions by ASCRI and Preqin for the return on its funds and transactions (For more information, visit www.inveready.com).