RiverVest Venture Partners’ Post

🌟 Unlocking the Power of Partial Agonists 💊💡 Partial agonists, the unsung heroes of pharmacology, possess a distinct quality that sets them apart from their full agonist counterparts. Unlike full agonists, partial agonists exhibit a partial activation response (submaximal response), striking a delicate balance between agonism and antagonism. 💥 The Magic of Partial Activation: A Balancing Act 🔍 Partial agonists act as versatile modulators, fine-tuning receptor activity to achieve desired therapeutic outcomes. Their ability to exert a moderate effect allows for precise control over physiological processes, minimizing side effects and optimizing treatment efficacy. 🔬 From the realm of psychiatry to pain management, partial agonists play a pivotal role in a diverse array of therapeutic interventions. 1. Aripiprazole: Revolutionizing schizophrenia treatment with its unique partial agonist activity at dopamine receptors. 2. Buprenorphine: Offering a safer alternative for opioid dependence management, thanks to its partial agonist activity at mu opioid receptors. By embracing the versatility of partial agonists, we can revolutionize pharmacotherapy and pave the way for innovative treatment approaches. #Pharmacology #PartialAgonists #Therapeutics

🔗 My 2 cent on the FDA advisory committees responses to Lykos echoes many other psychedelic researchers/neuropsychopharmacologists view on the clear added benefit of mechanistic data to support the clinical data. 🧠 Neuroimaging data to test candidate mechanisms of change following psychedelic therapy through fMRI/PET/EEG may provide an additional objective way of examining the therapeutic response. 📈 Importantly, imaging can help to identify differences in the brains responses to placebo and treatment arms, thereby providing hard evidence for how therapeutic clinical effects may come about. 🏥 Indeed, when this was discussed recently with the European Medicines Agency, they responded that the totality of the evidence base would be considered when assessing psychedelic therapy eg: clinical trial, neuroimaging and mechanism of action data and real world evidence. It is clear we must advance our scientific approach to psychedelic clinical trials and neuroscience provides a robust way to optimise psychedelic drug development. A paper on how to do this led by Matthew Wall and our team demonstrates how we can make a start.

"CONCLUSIONS Hypermetabolism is likely pathogenic in depression, with its magnitude in direct proportion to the severity of depressive symptoms. It is brain-wide, with disproportionate increases in cortical and subcortical attentional networks, particularly in women and older patients. Future Cerebral Blood Flow (CBF) studies should be sufficiently large to permit assessment of regional flow without whole brain Cerebral Blood Flow (wbCBF) normalization, and they should include participants with a full range of clinical presentations to ensure findings generalize to real-world patients. SSRIs are associated with lower regional Cerebral Blood Flow (rCBF), which may account in part for their therapeutic effects. Hypermetabolism may be a reasonable target for novel therapeutics in MDD" https://lnkd.in/g8Yk4mVk

Cybin Inc. recently shared compelling updates at the 2024 American College of Neuropsychopharmacology (ACNP) Annual Meeting, showcasing the potential of its leading investigational therapeutic, CYB003, a deuterated psilocybin analog. The company’s poster presentations highlighted 12-month efficacy results of CYB003 in treating Major Depressive Disorder (MDD), demonstrating durable symptom reduction. These findings underscore Cybin’s commitment to addressing unmet mental health needs through innovative and scientifically rigorous approaches. “The ACNP annual meeting is an excellent opportunity to share the rapid clinical progress Cybin is making across our deuterated psilocin and DMT programs,” said Doug Drysdale, Chief Executive Officer of Cybin Inc. This milestone reflects Cybin’s leadership in developing next-generation therapeutics aimed at transforming mental health care. Learn more about Cybin’s latest research and ongoing mission: Business Wire. #MentalHealth #Neuropsychopharmacology #CYB003 #DepressionTreatment #Biotechnology #ACNP2024 #CybinTherapeutics

𝐄𝐯𝐞𝐜𝐱𝐢𝐚 𝐓𝐡𝐞𝐫𝐚𝐩𝐞𝐮𝐭𝐢𝐜𝐬 𝐂𝐨𝐦𝐩𝐥𝐞𝐭𝐞𝐬 𝐏𝐫𝐞-𝐈𝐍𝐃 𝐌𝐞𝐞𝐭𝐢𝐧𝐠 𝐟𝐨𝐫 𝐄𝐕𝐗-𝟏𝟎𝟏 𝐰𝐢𝐭𝐡 𝐅𝐃𝐀 Evecxia Therapeutics Evecxia Therapeutics, Inc., the first company focused on Serotonin Synthesis Amplification, has successfully completed a pre-IND meeting with the FDA’s Division of Psychiatry regarding EVX-101, a novel adjunctive antidepressant for patients who respond inadequately to serotonin reuptake inhibitors (SSRIs). Key outcomes from the meeting include: No concerns raised regarding non-clinical GLP safety data or Phase 1 safety, tolerability, and pharmacokinetics. Guidance received on non-clinical development, with some elements omitted given the safety history of 5‑HTP, EVX-101’s key ingredient. Alignment achieved with the FDA on plans to submit an IND for a Phase 2 trial. CEO Jacob Jacobsen Jacob Pade Ramsøe Jacobsen commented: "This positive feedback from the FDA marks a key milestone in advancing EVX-101 as a safer, more effective treatment for patients with depression not responding to SSRIs." #MentalHealth #FDA #Biotech #DepressionTreatment #CNSDisorders #DrugDevelopment #ClinicalTrials #LifeSciences

The potential for GLP-1 receptor agonists to help with alcohol use disorders has emerged from various observations and preliminary studies: 1. Anecdotal Reports: Many of my patients taking GLP-1 RAs like semaglutide (Ozempic, Wegovy, Rybelsus) have reported unintended reductions in alcohol consumption. 2. Social Media Reports: Reports often come from social media and other informal sources, indicating a potential link between GLP-1 RAs and decreased alcohol use. 3. Preclinical Studies: Animal studies have shown that GLP-1 RAs can reduce alcohol intake. For instance, research on rodents has demonstrated that GLP-1 receptor stimulation can decrease alcohol consumption and seeking behavior, suggesting a possible effect on alcohol-related neural pathways. 4. Mechanistic Insights: GLP-1 receptors are located in brain regions associated with reward and addiction, such as the nucleus accumbens. Activation of these receptors may influence the neurobiological processes underlying addiction, including satiety, craving, and aversion. 5. Clinical Observations: Some clinicians have noted reduced alcohol consumption in patients being treated with GLP-1 RAs for diabetes or obesity, leading to further interest in these medications for alcohol use disorder treatment. 6. Ongoing Clinical Trials: There are now clinical trials underway specifically investigating the effects of GLP-1 RAs on alcohol use disorders. These trials aim to provide more rigorous evidence and understand the underlying mechanisms. 7. Potential Neurobehavioral Mechanisms: The observed reductions in alcohol use may be due to several neurobehavioral mechanisms influenced by GLP-1 RAs, such as altered reward processing, reduced craving and preoccupation with alcohol, enhanced satiety, and changes in subjective responses to alcohol. Stay tuned! GLP RA's may be the next revolutionary medication for Psychiatry! #GLP1ReceptorAgonists #AlcoholUseDisorder #Semaglutide #Ozempic #Wegovy #Rybelsus #AddictionTreatment #Pharmacovigilance #DrugRepurposing #MentalHealth #Neurobiology #ClinicalResearch #HealthcareInnovation #MedicalScience #PatientCare #AddictionRecovery #HealthTech #MedicalResearch #BehavioralHealth #empathymindcare #empathyminded

AbbVie's $2B-Plus Deal with Gilgamesh Pharmaceuticals Shaping the Future of Psychiatric Therapies The collaboration aims to harness Gilgamesh's innovative neuroplastogen science to develop novel compounds that enhance neuroplasticity, offering new hope in the treatment of mood and anxiety disorders. By leveraging Gilgamesh's expertise in neuroplastogen research, AbbVie aims to pioneer innovative treatment approaches that could transform the landscape of psychiatric care.  Jonathon Sedgwick, Ph.D., senior vice president and global head of discovery research at AbbVie, expressed enthusiasm about the collaboration, stating, "We look forward to working with Gilgamesh's world-class team to advance the development of novel neuroplastogens and pave the way for additional treatment approaches in psychiatry.” Share your thoughts on how this collaboration will impact the future of psychiatric therapies. Read more in the article in the comment below. #Biotech #PsychiatricTherapies #AbbVie #GilgameshPharma #NeuroplastogenScience #MentalHealth #Pharmaceuticals #Collaboriation #FDA #Health

This week's #EditorsSpotlight 💡 Yazen Alnefeesi and co-authors explore ligands of the trace amine-associated receptors (TAARs) as a new class of anxiolytics. Most current #anxiety treatments, such as benzodiazepines and serotonin reuptake inhibitors, come with side effects that often impact patient compliance. Preclinical studies suggest that TAARs, particularly TAAR1, TAAR2, and TAAR5, play key roles in anxiety regulation, with effects on neurogenesis and plasticity in brain regions like the amygdala and hippocampus. 🧠 Ulotaront, a TAAR1 agonist, is currently being investigated in clinical trials for generalized anxiety disorder. Could this represent a breakthrough in anxiety treatment? 🤯 #Neuroscience #MentalHealth #Anxiety #Research #Pharmacology Find out more on: https://lnkd.in/d3RHctDJ

🌈 Unlocking the Potential of Psychedelics: A Breakthrough in Neuropsychiatric Treatment! 🌟 This time I was browsing through neuroscience news and latest research and came across a new interesting article about the psychedelics 😵💫🧠 Recent research has shed light on the therapeutic promise of psychedelic substances like lysergic acid diethylamide (LSD) and psilocybin for various neuropsychiatric disorders. But here's the twist: it's not just about serotonin (5-HT) receptor 5-HT2A – another player, 5-HT1A, is emerging as a key influencer in the effects of psychedelics, especially 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) found in Colorado River toad toxin. 🔬 What Was Discovered : Through cutting-edge cryogenic electron microscopy (cryo-EM) techniques, medicinal chemistry, and behavioral studies in mice, researchers delved deep into the molecular mechanisms of 5-MeO-DMT pharmacology. By analyzing the structure–activity relationships of 5-methoxytryptamines, they identified the molecular determinants of 5-HT1A signaling potency, efficacy, and selectivity. ⚗️ Why It Matters: Understanding how psychedelics engage with 5-HT1A could pave the way for novel treatments for neuropsychiatric disorders. By contrasting the effects of 5-MeO-DMT and its analogues with clinically used medications, including LSD and 5-HT1A agonists, researchers are uncovering new avenues for drug development. 🌱 The Future: Here's the game-changer – a 5-HT1A-selective analogue of 5-MeO-DMT exhibits anxiolytic-like and antidepressant-like effects without the hallucinogenic properties. This could mean a leap forward in developing safer, more effective medications for mental health conditions. 🔥 Controversial Terrain : These groundbreaking findings enter the realm of controversy, challenging conventional perspectives on mental health treatment. Public opinion on the use of psychedelics for therapy varies widely, with some embracing their potential while others express concerns about safety and legality. Additionally, government policies around the world regarding the use of psychedelics in medical research and treatment are complex and often restrictive, adding layers of challenge to further exploration and implementation. But let’s be optimistic 🤓 Let's continue to explore the therapeutic potential of psychedelics and push the boundaries of neuropsychiatric treatment together, navigating the complexities with care and diligence! 🚀 #Psychedelics #Neuroscience #MentalHealth #Research #Innovation #Depression #DMT

I am pleased to share a link to a #bioRxiv pre-print that describes collaborative research work between my group and the group of Panos Roussos at the Icahn School of Medicine. By analyzing specimens from the prefrontal cortex of #schizophrenia (SCZ) and #bipolardisorder (BD) cases and controls, we generated several findings including: • MicroRNA isoforms (#isomiRs), transfer RNA-derived fragments (#tRFs), ribosomal RNA-derived fragments (#rRFs), and Y RNA-derived fragments (#yRFs) account for 98% of all small RNAs in these specimens. • Small RNAs participate in rather complex regulatory networks and their changes in SCZ and BD mimic the changes occurring in normal brain aging. • Unexpectedly, #tRFs, #rRFs, and #yRFs appear more important than #microRNAs / #isomiRs in this context. Link to the full pre-print 👇 https://lnkd.in/ePV2QNJ4