β2-adrenergic receptor

Drug Combination’s Unique Mechanism of Action Enables Reactivation of Brain Adrenergic Function, Showing Improvements in Multiple Areas of Cognition SAN CARLOS, Calif. & LISBON, Portugal--(BUSINESS WIRE)-- CuraSen Therapeutics, Inc., a clinical-stage company developing small molecule therapies to treat neurodegenerative disease, announced that it will present additional positive Phase 2a data with its combination adrenergic activator, CST-2032/CST-107, in patients with mild cognitive impairment (MCI) or mild dementia from either Alzheimer’s or Parkinson’s disease. The oral presentation will take place at AD/PD™ 2024: The International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders, being held March 5-9, 2024, in Lisbon, Portugal. CST-2032 is one of CuraSen’s two lead product candidates being tested in patients with Alzheimer’s and Parkinson’s disease. Both CST-2032 and CST-103, the company’s other lead clinical candidate, are oral, brain-permeant, beta2 adrenoceptor (β2-AR) agonists delivered in combination with CST-107 (nadolol, a brain-sparing beta blocker) to inhibit peripheral effects of β2-AR agonism. Both CST-2032 and CST-103 work by enabling reactivation of brain adrenergic function lost early in the neurodegenerative disease process. The updated Phase 2a data with CST-2032/CST-107 showed statistically and clinically important effects across several cognitive domains in patients with Alzheimer’s and Parkinson’s disease, such as memory, attention, executive function, facial recognition and impulse control — areas known to be impacted by adrenergic function. Target effect sizes of 0.2-0.3 or higher, as seen in this study, predict success in larger, longer studies. “These encouraging data build on earlier results presented at October 2023’s CTAD conference, reinforcing that treatment with CST 2032/CST-107 can produce meaningful quality-of-life cognitive improvements for Alzheimer’s and Parkinson’s patients, particularly those with mild cognitive impairment, rapidly and safely,” said Anthony Ford, PhD, chief executive officer of CuraSen. “The robust, collective data set from both CST-2032 and CST-103 demonstrate that this novel mechanism of action for restoring adrenergic function to the brain is a highly compelling strategy to address unmet symptoms of neurodegeneration. We plan to evaluate additional doses and refine optimal patient profiles in our upcoming Phase 2 studies, with the goal to significantly increase cognitive performance and ultimately, halt disease progression.” The randomized, placebo-controlled, double-blinded crossover study evaluated 64 patients with MCI or mild dementia from either Alzheimer’s disease or Parkinson’s diseases: AD with MCI = 30 patients randomized; 25 completed AD with dementia = 6 patients randomized; 5 completed PD with MCI = 22 patients randomized; 21 completed PD with dementia = 6 patients randomized; 4 completed Data highlights included: Digit Symbol Substitution test, which measures complex attention, memory and executive function: AD patients with MCI = 0.36 effect size; p=0.02 on Day 14 Facial Expression Recognition response time to accurately recognize facial expressions, which measures social cognition: AD patients with MCI = 0.66 effect size; p=0.04 on Day 14 for happy expression and 0.91 effect size; p = 0.01 on Day 14 for surprise expression Stop Signal test, which measures impulse control PD patients with MCI = 0.52 effect size; p=0.04 on Day 14 Excellent safety and tolerability pro /> No serious adverse events: no increases in heart rate observed one to four hours after dose The company plans to initiate longer studies with both CST-2032/CST-107 and CST-103/CST-107 in AD and PD patients with MCI later this year, as well as develop fixed-dose combination tablets for each of these drug candidates. Study Objectives and Design The study objectives were to establish safety and tolerability of CST-2032/CST-107, identify optimal dosing, and identify cognitive tests responsive to agonist stimulus within the two-week dosing period. Measures of cognition included the digit symbol substitution test, Cambridge neuropsychological test battery, and the facial expression recognition task. The study took place at multiple sites in the United States and New Zealand. Patients received either daily 3 mg of CST-2032 with 3 mg of nadolol for 14 days, or matching placebo, followed by a wash-out period (≥7-d) before crossing over to the other treatment arm. Blood samples are being analyzed for AD biomarkers, and DNA samples for AD and PD genotyping. Abstract Details Title: “CST-2032, a Novel Beta-2 Adrenoceptor Agonist, Improves Cognition in Patients with Impairment Due to Alzheimer’s or Parkinson’s Disease” Abstract #: PO34 Presenter: Gabriel Vargas, MD, PhD, chief medical officer, CuraSen Therapeutics Session: Translational Drug Discovery and Experimental Models 05 Date: Saturday, March 9, 2024 Time: 17:25-17:40 UTC, session time,16:40 - 18:40 UTC Location: Auditorium VII About CuraSen Therapeutics CuraSen is focused on the development of new treatments for neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease and other related orphan conditions. CuraSen’s drugs are designed to activate certain receptor populations in the brain to compensate for critical neuronal and glial functions that have otherwise been lost due to degeneration and represent a unique approach in the field. The company is evaluating CST-103 and CST-2032, both selective β2-AR agonists, in combination with CST-107, a β-AR blocker, in multiple Phase 2 clinical studies. CST-3056, an α1A-AR agonist, is in preclinical development for the treatment of Alzheimer’s disease. For more information, please visit .

neffy demonstrated statistically significant and clinically meaningful improvement in pruritus, hives, body surface area and erythema in treatment-resistant chronic spontaneous urticaria patients, a skin disorder that causes itchy hives and/or angioedema Data supports continued development of neffy in urticaria with planned outpatient study in acute flares to initiate during 2024, with pivotal study to potentially initiate in 2025 Feb. 26, 2024 -- ARS Pharmaceuticals, Inc. (NASDAQ: SPRY), a biopharmaceutical company dedicated to empowering at-risk patients and caregivers to better protect patients from severe allergic reactions that could lead to anaphylaxis, today announced positive efficacy results in its phase 2 inpatient chronic spontaneous urticaria study with neffy (epinephrine nasal spray), an investigational new drug. The trial met its primary endpoints with both 1 mg and 2 mg neffy demonstrating statistically significant and clinically meaningful changes from baseline in itch, hives, urticaria and erythema scores as early as 5 minutes after dosing. Urticaria is a skin disorder that causes itchy hives and/or angioedema; 50% of chronic urticaria cases1 are non-responsive to first-line antihistamine therapy. These data for neffy are being presented in an oral presentation today, February 26, at 1:10 pm ET at the 2024 American Academy of Allergy, Asthma and Immunology (AAAAI) in Washington, D.C. in Room 207B (Level 2) of the Convention Center. “The Phase 2 results in this highly refractory patient population are impressive and encouraging as they indicate neffy could be a game-changing therapeutic advance in the treatment of urticaria,” says David Bernstein, M.D., Emeritus Professor of Pediatrics at the Cincinnati Children’s Hospital Medical Center, a former member of the Joint Task Force on Practice Parameters (urticaria guidelines) and Principal Investigator of the Study, “Urticaria symptoms clear within minutes after dosing, and neffy could offer patients a novel treatment option to address existing gaps in the efficacy of currently available antihistamines or biologics.” The EPI-U01 study was a randomized, placebo-controlled, cross-over study evaluating the safety and efficacy of epinephrine nasal spray in patients with chronic spontaneous urticaria (CSU) treated with chronic medications who were still experiencing flares. This oral presentation includes data analysis from 18 adult patients as of the cut-off date who enrolled in this study and returned to the clinical site while experiencing a flare, where they were randomized to receive either a single treatment of 1 mg or 2 mg neffy or placebo in a crossover design. All subjects had flares with pruritus and hives scores greater than or equal to 2 on a 3 point severity scale, despite all patients having been treated with antihistamines or Xolair. There was no meaningful difference in efficacy on patient-reported itch severity score, patient-reported hives severity score, investigator-related extent of urticaria, or investigator-related erythema score between 1 mg and 2 mg neffy doses, indicating that the 1 mg dose may be sufficient to activate the beta-2 adrenergic receptors responsible for stopping the mast cell degranulation and allergic mediator release that leads to an urticaria flare. neffy was well-tolerated, with adverse events reported in 8 subjects, which were all mild or moderate in severity. The most common adverse event reported was nasal discomfort in 5 subjects. There were no serious adverse events. “This study adds to the wealth of data supporting the efficacy and safety of neffy in the treatment of type I allergic reactions,” said Sarina Tanimoto, M.D., Ph.D., Chief Medical Officer and Co-Founder of ARS Pharma. “Urticaria is not only a standalone type I allergy disease, but also represents the most frequent symptom observed during type I allergic reactions including anaphylaxis. The improvement in urticaria symptoms almost immediately after dosing neffy demonstrated its rapid onset of action, and is consistent with the previously reported responses on pharmacodynamic markers of efficacy in as little as one minute after dosing.” Urticaria is a skin disorder driven by mast cell degranulation and histamine release, which causes itchy wheals (hives) and angioedema, or both. In the United States, the annualized incidence is approximately 5 million cases (1.56 per 100,000).2 Less than 40% of cases become chronic urticaria, which can last for several years before spontaneous remission occurs.2 Antihistamines are the first-line therapy for treatment of urticaria, but 20 to 25% of acute urticaria cases1, and 50% of chronic urticaria cases3 are non-responsive to antihistamines. These non-responsive patients on stable therapy regimens can experience exacerbations or flares several times a year among acute cases, and even several times a week4, including up to 3 or 4 emergency room visits, among chronic urticaria cases.5 Angioedema is also a co-occurring symptom in about 33 to 67% of these patients.6 There are currently no approved community use treatments for acute flares experienced by urticaria patients on chronic regimens of antihistamines. neffy may provide episodic symptomatic relief of these acute flares or exacerbations to improve the quality of life of urticaria patients. Patients would have the option to quickly resolve exacerbations or flares at home without escalating to chronic use of systemic biologics that may have more serious side effects and benefit-risk considerations, or having to visit the emergency room for further treatment. ARS Pharma plans to initiate a placebo-controlled outpatient urticaria study in patients treated with antihistamines who experience frequent acute flares later in 2024 followed by the potential initiation of a single pivotal efficacy study in 2025. This would follow the anticipated FDA approval of neffy for allergic reactions (Type I) including anaphylaxis in the second half of 2024. Type I severe allergic reactions are serious and potentially life-threatening events that can occur within minutes of exposure to an allergen and require immediate treatment with epinephrine, the only FDA-approved medication for these reactions. While epinephrine autoinjectors have been shown to be highly effective, there are well published limitations that result in many patients and caregivers delaying or not administering treatment in an emergency situation. These limitations include fear of the needle, lack of portability, needle-related safety concerns, lack of reliability, and complexity of the devices. There are approximately 40 million people in the United States who experience Type I severe allergic reactions. Of those, only 3.3 million currently have an active epinephrine autoinjector prescription, and of those, only half consistently carry their prescribed autoinjector. Even if patients or caregivers carry an autoinjector, more than half either delay or do not administer the device when needed in an emergency. ARS Pharma is a biopharmaceutical company dedicated to empowering at-risk patients and caregivers to better protect themselves from severe allergic reactions that could lead to anaphylaxis. The Company is developing neffy® (previously referred to as ARS-1), an intranasal epinephrine product in clinical development for patients and their caregivers with Type I allergic reactions including food, medications and insect bites that could lead to life-threatening anaphylaxis. For more information, visit www.ars-pharma.com. References: 1 Sanchez-Borges M et al. World Allergy Organization Journal 2014; 7, 1-5, Williams, PV et al. Dermatol Ther 2018; 8(1):69-83, Maurer M et al. Clin Exp Allergy 2019; 49(5): 655-662 2 Kolkhir,P. et. al. Urticaria. Nat Rev Dis Primers 8, 61 (2022) 3 Seo JH & Kwon JW. Korean J Intern Med 2019; 34(2):418-425, Sanchez-Borges M et al. Allergologia et Immunopathologia 2015; 43(4): 409-415, Barniol C et al. Annals of Emergency Medicine 2018; 71(1): 125-131 4 Raciborski F, et al. Postepy Dermatol Allerg 2018; 35(1):67-73 5 Barniol C et al. Annals of Emergency Medicine 2018; 71(1): 125-131 6 Sussman G et al. Allergy 2018; 73(8): 1724-1734. 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SEOUL, Korea and REDWOOD CITY, Calif., Dec. 14, 2023 (GLOBE NEWSWIRE) -- GPCR Therapeutics, Inc., a clinical-stage international biopharmaceutical company, announces it enters into an out-licensing agreement with Bridge Biotherapeutics (KQ288330) for the CXCR4-LPA1 inhibitor combination method of treatment. GPCR receives an upfront payment of KRW 2 billion (approx. USD 1.5 million), and a 50:50 profit-share on future commercialization, including sub-licenses. In collaboration with Bridge Biotherapeutics, GPCR will pursue joint development and commercialization of the combination therapy. Conducting a multinational phase 2a clinical trial of BBT-877, an autotaxin inhibitor for the treatment of IPF, Bridge Biotherapeutics has been accelerating development of its proprietary IPF pipeline. Last September, GPCR published the paper on the direct interaction between two different GPCRs, CXCR4 and LPA1, in the peer-reviewed academic journal ‘Cell Communication and Signaling’(1). The target GPCRs are known to promote fibrotic diseases such as idiopathic pulmonary fibrosis (IPF). Through various in vitro experiments, the company found that the efficacy of LPA1 inhibition can be further maximized by inhibition of CXCR4, thereby securing a scientific basis that the CXCR4- LPA1 inhibitor combination may be necessary for full anti-fibrotic activity. Based on this finding, GPCR filed a provisional patent application on the CXCR4-LPA1 inhibitor combination method of treatment. Dr. Dong Seung Seen, founder and CEO of GPCR Therapeutics, commented, “Since the publication of our paper, various global companies have expressed interest in the relationship between LPA1 and CXCR4 and its inhibitory effect. Due to the versatility of our patent, we look forward to collaborating with many IPF-targeting companies, starting with Bridge Biotherapeutics.” James Lee, founder and CEO of Bridge Biotherapeutics, said, “We are encouraged to collaborate with GPCR Therapeutics to uncover new possibilities of IPF treatment. Our collaboration will help us move forward to identifying and bringing novel treatment of IPF, such as a combination therapy of LPA1 and CXCR4 inhibitor, based on GPCR’s latest research.” IPF is a progressive chronic lung condition that causes scarring (fibrosis) of a patients’ lungs which makes breathing increasingly difficult as the lungs become stiffer and lose their elasticity. The lungs become less efficient at transferring oxygen so that when someone with IPF breathes in, the transfer of oxygen through air sacs in their lungs and into their blood stream is impaired. Lung damage from IPF is irreversible, and there is currently no treatment that stops or reverses the scarring. In the US there are around 495 cases per 100,000 people, with median survival estimated at 2–5 years from the time of diagnosis. (2) (3) References (1) Cell Communication and Signaling paper, “LPA1-mediated inhibition of CXCR4 attenuates CXCL12-induced signaling and cell migration”: (2) American Lung Association data on IPF: (3) PubMed paper on incidence and prevalence of IPF: About GPCR Therapeutics GPCR Therapeutics, Inc. is a clinical-stage international biopharmaceutical company with an innovative approach to developing therapeutics built on its proprietary GPCR data. The company’s lead small molecule asset, GPC-100/Burixafor, targets CXCR4, one of the most prevalent chemokine GPCRs overexpressed in various cancers. The company has an ongoing US Phase 2 clinical trial assessing the efficacy of the combination of GPC-100 and propranolol in patients with multiple myeloma. In addition, the company is engaged in active collaborations with domestic and international biotechnology companies. By targeting the unique pharmacology of GPCR pairs, the company aims to develop life-changing treatments for cancer and other diseases. The company has identified that CXCR4 interacts with the beta-2 adrenergic receptor (B2AR), and this GPCR pair presents an alternate signaling pathway that is synergistically dependent on CXCR4 and B2AR activation. GPCR Therapeutics has its HQ in Seoul, Korea with additional R&D facilities in the San Francisco Bay Area, USA. For more information, visit gpcr.co.kr and follow us on LinkedIn. For more information, please contact: GPCR Therapeutics (in Seoul) DaYoon Kim - Business Development Manager Tel: +82-2-878-2848 dayoon.kim@gpcr.co.kr Scius Communications (in London): Katja Stout - Founder & Managing Partner +44 778 943 5990 katja@sciuscommunications.com Daniel Gooch - Partner +44 774 787 5479 daniel@sciuscommunications.com About Bridge Biotherapeutics, Inc. Bridge Biotherapeutics Inc., based in the Republic of Korea and the U.S., is a publicly traded, clinical-stage biotech company founded in 2015. Bridge Biotherapeutics is engaged in the discovery and development of novel therapeutics, focusing on therapeutic areas with high unmet needs, including fibrotic diseases and cancers. The company is developing BBT-877, a novel autotaxin inhibitor for the treatment of fibrotic diseases including idiopathic pulmonary fibrosis (IPF), and BBT-207, a potent targeted cancer therapy for non-small cell lung cancer (NSCLC) with EGFR C797S mutations. Learn more at