GPCR x CB2 x CB1

None InMed Pharmaceuticals (Nasdaq:INM) recently released preclinical data indicating its proprietary, small molecule compound, INM-901, targets multiple biological pathways associated with Alzheimer’s disease. Among the most interesting data from these studies was the ability of its compound to extend the length of neurites, which may indicate enhanced neuronal functioning in the brain and the potential to reverse the damage caused by Alzheimer’s disease. The company was encouraged with these breakthrough preclinical results and will be advancing the development of the INM-901 Alzheimer’s disease program. INM-901 May Address Multiple Pathologies Related to Alzheimer’s Disease InMed’s in vitro and in vivo studies demonstrated encouraging effects in a well-characterized Alzheimer’s disease preclinical model. In this study, InMed’s INM-901 demonstrated neuroprotective effects by reducing cell death in an amyloid-beta-induced cytotoxicity study and demonstrated an ability to promote the growth and extension of neurites (neuritogenesis), an essential component of cell-to-cell communication. INM-901 also demonstrated reduced neuroinflammation and showed improvement in behavior, cognitive function and memory in in vivo studies.   These promising early data of INM-901 represent the potential for disease-modifying effects as well as the potential to reverse neuronal damage associated with Alzheimer’s disease. InMed’s Senior VP of Preclinical Research and Development, Dr. Eric Hsu, is encouraged by the results indicating INM-901 may target multiple pathologies. “There continues to be a major unmet medical need for this multi-factorial disease and differentiated therapeutic mechanisms may play an important role. We believe the development of INM-901 may address several pathological factors including neuroinflammation, neuroprotection and neuritogenesis.” Study Reveals InMed’s INM-901 Targets CB1, CB2 and PPAR Pathways Research indicates that activating the endocannabinoid 1 (CB1) and endocannabinoid 2 (CB2) receptors may induce neuroprotective effects that may help protect brain cells from damage and death. Enhancing the natural activity at these receptors may help to slow the progression of Alzheimer’s disease, in which neuronal cell death is a hallmark.  CB1 and CB2 receptors are part of the endocannabinoid system which is involved in almost every facet of the body’s functioning and plays a key role in brain function. Activation of these receptors may address factors influencing Alzheimer’s disease progression. Studies of INM-901 demonstrate that this small molecule drug candidate acts as a preferential signaling ligand for CB1/CB2 and impacts the peroxisome poliferator-activated receptor (PPAR) signalling pathway. InMed’s INM-901 May Be Delivered Via Oral Administration InMed’s INM-901 is a small molecule, orally available drug candidate. Importantly, INM-901 appears to safely and effectively cross the blood/brain barrier, which is essential to any compound targeting diseases such as Alzheimer’s. The drug delivery options of small molecules could greatly reduce treatment costs and the compliance challenges associated with large molecule antibody therapies. Alzheimer’s Disease Presents a Major Unmet Medical Need Alzheimer’s is a complex neurodegenerative disease and its progression is caused by several pathological factors. A multifaceted approach is needed to effectively address its diverse causes and symptoms. According to the Alzheimer’s Association, an estimated 6.9 million Americans aged 65 and older are living with Alzheimer’s, about two-thirds of them are women. Alzheimer’s disease is the fifth leading cause of death amongst the elderly and the healthcare cost is substantial at an estimated $360 billion in the U.S. alone with another estimated $350 billion in unpaid care. Until recently, there were few treatment options available for those living with Alzheimer’s disease. Previously, patients could only turn to cholinesterase inhibitors that were intended to improve cognitive and behavioral symptoms. New, recently approved treatments are showing disease-modifying effects that aim to reduce the build-up of amyloid-beta plaques, a hallmark of Alzheimer’s disease. While these long-awaited treatments offer hope to patients, major challenges exist for this class of large-molecule compounds. As large molecules, these antibody therapies are not orally available and must be delivered via intravenous infusion every two to four weeks. In addition, there are safety concerns around brain bleeding, requiring an MRI scan every 6-12 months. INM-901 has shown to be a potentially disease-modifying small molecule drug candidate presenting an attractive therapeutic pathway with encouraging preclinical results. Long-term behavioral, mechanisms of action and receptor interaction studies are underway with data read-out expected early in the second half of calendar 2024. Representatives from InMed will be attending the Alzheimer’s Association International Conference in Philadelphia, PA from July 28 to August 1, 2024. Watch this video presentation by InMed’s CEO, Eric A. Adams as he discusses the potential role of INM-901 in Alzheimer’s treatment.

Poster presentation details screening approach allowing selection of candidate molecules applicable to dry eye disease and chronic ocular pain, with potential to identify therapeutic candidates with novel mechanisms of action for other ocular pathologiesSAN DIEGO, May 10, 2024 (GLOBE NEWSWIRE) -- Skye Bioscience, Inc. (Nasdaq: SKYE) (“Skye”), a clinical-stage biotechnology company focused on the discovery, development and commercialization of novel classes of therapeutic drugs that modulate the endocannabinoid system (ECS), today announced that it presented new data in a poster titled “Development and screening of a novel library of synthetic endocannabinoid agonists and inhibitors to advance a potential therapy to treat dry eye disease and chronic ocular pain” on May 9th at the ARVO (Association of Research in Vision and Ophthalmology) 2024 Annual Meeting. “The endocannabinoid system offers unique opportunities to address unmet medical needs with new mechanisms of action. At ARVO we showcased Skye’s development and screening of a novel library of synthetic agonists and inhibitors that could potentially fulfill some of these opportunities,” said Punit Dhillon, Chief Executive Officer and Chairman of Skye. Key highlights Presented biological ECS screening program focused on pathways relevant to dry eye disease (DED) and chronic ocular painThree synthetic cannabinoid-based compounds relevant to DED and chronic ocular pain have been identified for further pharmaceutical developmentConclusion: a unique screening approach has the potential to provide a new class of therapeutics with novel mechanisms of action for the treatment of diverse ocular pathologies. Chris Twitty, PhD, Chief Scientific Officer of Skye, added: “Skye’s strategy is to develop advanced pharmaceutical drugs capable of modulating the endocannabinoid system to positively impact ocular pathologies. The study’s evaluation of a novel synthetic cannabinoid-based library with biologically relevant cell types, targets, and pathways enabled the selection of candidate molecules applicable to DED and chronic ocular pain. Ultimately, we selected cannabinerol and two non-electrophilic indolic adducts of cannabidiolquinone and cannabigeroquinone that warrant further interrogation and pharmaceutical development.” Study details A rigorous in vitro screening platform based on modulation of pathways relevant to cannabinoid biology in the context of ocular pathologies was designed to interrogate a library of 98 synthetic cannabinoid-based molecules for their potential to treat ocular diseases. Immortalized human ocular cell lines and stable modified HEK cells were used to measure activation/inhibition of specific cannabinoid receptors, including CB1, CB2, GPR55, and TRPV1. The library was initially interrogated using a threshold of relevant biological activity. The resulting 38 compounds were scored based on EC50/IC50 of signaling (CB1/2/TRPV1/PPARg/NF-kB) and inhibition of ROS and HIF-1a in human epithelial and endothelial (corneal/conjunctival) cells. These compounds were also interrogated for chemical/developability attributes, which helped provide the rationale for ultimately selecting three lead candidate molecules. About Skye Bioscience Skye is focused on unlocking the pharmaceutical potential of the endocannabinoid system to treat diseases with metabolic, inflammatory, and fibrotic processes. Backed by leading life science venture investors, Skye's strategy leverages biologic targets with substantial human proof of mechanism for the development of first-in-class therapeutics with significant clinical and commercial differentiation. Nimacimab, a negative allosteric modulating antibody that inhibits peripheral CB1, showed a favorable safety and tolerability profile in a Phase 1 study. Skye plans to start a Phase 2 clinical trial in obesity comparing monotherapy and combination arms of Nimacimab and a GLP-1R agonist in mid-2024. Enrollment has been completed for a Phase 2 clinical trial of SBI-100 Ophthalmic Emulsion, a CB1 agonist currently being studied in patients with glaucoma and ocular hypertension. Topline data for this study is expected in Q2 2024. For more information, please visit: https://www.skyebioscience.com. CONTACTInvestor Relationsir@skyebioscience.com(858) 410-0266 LifeSci Advisors, Mike Moyermmoyer@lifesciadvisors.com617-308-4306 Media InquiriesLifeSci Communications, Michael Fitzhughmfitzhugh@lifescicomms.com(628) 234-3889 FORWARD LOOKING STATEMENTSThis letter contains forward-looking statements, including statements regarding our product development, business strategy, the timing of clinical trials, and commercialization of cannabinoid-derived therapeutics. Such statements and other statements in this press release that are not descriptions of historical facts are forward-looking statements that are based on management’s current expectations and assumptions and are subject to risks and uncertainties. If such risks or uncertainties materialize or such assumptions prove incorrect, our business, operating results, financial condition, and stock price could be materially negatively affected. In some cases, forward-looking statements can be identified by terminology including “anticipated,” “plans,” “goal,” “focus,” “aims,” “intends,” “believes,” “can,” “could,” “challenge,” “predictable,” “will,” “would,” “may” or the negative of these terms or other comparable terminology. We operate in a rapidly changing environment, and new risks emerge from time to time. As a result, it is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements the Company may make. Risks and uncertainties that may cause actual results to differ materially include, among others, our capital resources, uncertainty regarding the results of future testing and development efforts and other risks that are described in the Risk Factors section of Skye’s most recent annual or quarterly report filed with the Securities and Exchange Commission. Except as expressly required by law, Skye disclaims any intent or obligation to update these forward-looking statements.

Designation Based on Pre-Clinical Data and Initial Clinical Data from the Company's MAvERIC-Pilot Phase II Study This is a Designated News Release. Toronto, Ontario--(News - February 15, 2024) - Cardiol Therapeutics Inc. (NASDAQ: CRDL) (TSX: CRDL) ("Cardiol" or the "Company"), a clinical-stage life sciences company focused on the research and clinical development of anti-inflammatory and anti-fibrotic therapies for the treatment of heart disease, announces that the United States Food and Drug Administration ("FDA") has granted Orphan Drug Designation ("ODD") for the Company's lead small molecule drug candidate for the treatment of pericarditis, which includes recurrent pericarditis. CardiolRx™ is currently in Phase II clinical trials for recurrent pericarditis and acute myocarditis. "The FDA's decision was based on pre-clinical data combined with initial clinical data from the Company's MAvERIC-Pilot Phase II study," commented Dr. Andrew Hamer, Cardiol Therapeutics' Chief Medical Officer and Head of Research & Development. "This designation reinforces the potential of CardiolRx™ to improve the lives of patients suffering with recurrent pericarditis, a debilitating heart disease associated with symptoms that adversely affect quality of life and physical activity." The FDA grants ODD to a drug or biological product to prevent, diagnose, or treat a rare disease or conditions that affect fewer than 200,000 people in the United States. ODD provides benefits to sponsors including potential seven-year marketing exclusivity, exemptions from certain FDA fees, and tax credits for qualified clinical trials. Products with ODD may also qualify for accelerated regulatory review via Fast Track, Breakthrough Therapy, or Priority Review designations. MAvERIC-Pilot (NCT05494788) is a Phase II open-label pilot study investigating the tolerance, safety, and effect of CardiolRx™ administered to patients with recurrent pericarditis. In addition to standard safety assessments, MAvERIC-Pilot is designed to evaluate improvement in objective measures of this rare disease. The primary efficacy endpoint is the change, from baseline to eight weeks, in patient-reported pericarditis pain using an 11-point numeric rating scale ("NRS"). The NRS is a validated clinical tool employed across multiple conditions with acute and chronic pain, including previous studies of recurrent pericarditis. Secondary endpoints include the NRS score after 26 weeks of treatment, and changes in circulating levels of C-reactive protein, a commonly used clinical marker of inflammation. Importantly, the study will assess freedom from pericarditis recurrence. Recurrent pericarditis refers to inflammation of the pericardium (the membrane or sac that surrounds the heart) that follows an initial episode (frequently resulting from a viral infection). Patients may have multiple recurrences. Symptoms include debilitating chest pain, shortness of breath, and fatigue, resulting in physical limitations, reduced quality of life, emergency department visits, and hospitalizations. Significant accumulation of pericardial fluid and scarring can progress to life-threatening constriction of the heart. The only FDA-approved therapy for recurrent pericarditis, launched in 2021, is costly and is primarily used as a third-line intervention. On an annual basis, the number of patients in the United States having experienced at least one recurrence is estimated at 38,000. Approximately 60% of patients with multiple recurrences (>1) still suffer for longer than 2 years, and one third are still impacted at 5 years. Hospitalization due to recurrent pericarditis is often associated with a 6-8-day length of stay and cost per stay is estimated to range between $20,000 and $30,000 in the United States. About Cardiol Therapeutics Cardiol Therapeutics Inc. (NASDAQ: CRDL) (TSX: CRDL) is a clinical-stage life sciences company focused on the research and clinical development of anti-inflammatory and anti-fibrotic therapies for the treatment of heart disease. The Company's lead small molecule drug candidate, CardiolRx™ (cannabidiol) oral solution, is pharmaceutically manufactured and in clinical development for use in the treatment of heart disease. It is recognized that cannabidiol inhibits activation of the inflammasome pathway, an intracellular process known to play an important role in the development and progression of inflammation and fibrosis associated with myocarditis, pericarditis, and heart failure. Cardiol has received Investigational New Drug Application authorization from the FDA to conduct clinical studies to evaluate the efficacy and safety of CardiolRx™ in two diseases affecting the heart: (i) a Phase II multi-center open-label pilot study in recurrent pericarditis (the MAvERIC-Pilot study; NCT05494788), an inflammatory disease of the pericardium which is associated with symptoms including debilitating chest pain, shortness of breath, and fatigue, and results in physical limitations, reduced quality of life, emergency department visits, and hospitalizations; and (ii) a Phase II multi-national, randomized, double-blind, placebo-controlled trial (the ARCHER trial; NCT05180240) in acute myocarditis, an important cause of acute and fulminant heart failure in young adults and a leading cause of sudden cardiac death in people less than 35 years of age. Cardiol is also developing a novel subcutaneously administered drug formulation of cannabidiol intended for use in heart failure - a leading cause of death and hospitalization in the developed world, with associated healthcare costs in the United States exceeding $30 billion annually. For more information about Cardiol Therapeutics, please visit cardiolrx.com. Cautionary statement regarding forward-looking information: This news release contains "forward-looking information" within the meaning of applicable securities laws. All statements, other than statements of historical fact, that address activities, events, or developments that Cardiol believes, expects, or anticipates will, may, could, or might occur in the future are "forward-looking information". Forward looking information contained herein may include, but is not limited to, statements relating to the Company's focus on developing anti-inflammatory and anti-fibrotic therapies for the treatment of heart disease, the molecular targets and mechanism of action of the Company's product candidates, the Company's intended clinical studies and trial activities and timelines associated with such activities, including for primary efficacy endpoint and secondary endpoints, the Company's plan to advance the development of a novel subcutaneous formulation of CardiolRx™ for use in heart failure, and the ODD reinforcing the potential of CardiolRx™ to improve the lives of patients suffering with recurrent pericarditis. Forward-looking information contained herein reflects the current expectations or beliefs of Cardiol based on information currently available to it and is based on certain assumptions and is also subject to a variety of known and unknown risks and uncertainties and other factors that could cause the actual events or results to differ materially from any future results, performance or achievements expressed or implied by the forward-looking information, and are not (and should not be considered to be) guarantees of future performance. These risks and uncertainties and other factors include the risks and uncertainties referred to in the Company's Annual Report on Form 20-F dated March 28, 2023, as well as the risks and uncertainties associated with product commercialization and clinical studies. These assumptions, risks, uncertainties, and other factors should be considered carefully, and investors should not place undue reliance on the forward-looking information, and such information may not be appropriate for other purposes. Any forward-looking information speaks only as of the date of this press release and, except as may be required by applicable securities laws, Cardiol disclaims any intent or obligation to update or revise such forward-looking information, whether as a result of new information, future events, or results, or otherwise. For further information, please contact: Trevor Burns, Investor Relations +1-289-910-0855 trevor.burns@cardiolrx.com To view the source version of this press release, please visit