A Phase 2b/3, Randomized, Double-Masked, Vehicle-Controlled Study Evaluating the Safety and Efficacy of Two Concentrations (0.4% and 1%) of ALY688 Ophthalmic Solution in Subjects With Dry Eye Disease (OASIS-1)

Study Evaluating the Safety and Efficacy of Two Concentrations (0.4% and 1%) of ALY688 Ophthalmic Solution in Subjects with Dry Eye Disease

Start Date19 May 2021

Sponsor / Collaborator

Allysta Pharmaceuticals, Inc.Startup

NCT04855565 / TerminatedPhase 1

Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Subcutaneous Doses of ALY688-SR in Generally Healthy Overweight or Obese Adults

First in human study of ALY688-SR administered as a subcutaneous injection

Start Date19 May 2021

Sponsor / Collaborator

Allysta Pharmaceuticals, Inc.Startup

[+1]

NCT04201574 / CompletedPhase 1/2

A Phase 1/2a, Randomized, Double-Masked, Vehicle-Controlled Study Evaluating the Safety and Exploratory Activity of Two Concentrations of ALY688 Ophthalmic Solution in Subjects With Dry Eye Disease

Clinical Trial Evaluating the Safety and Tolerability of ALY688 in Subjects with Dry Eye Disease

Start Date16 Dec 2019

Sponsor / Collaborator

Allysta Pharmaceuticals, Inc.Startup

100 Clinical Results associated with ALY-688

100 Translational Medicine associated with ALY-688

100 Patents (Medical) associated with ALY-688

Literatures (Medical) associated with ALY-688

01 Nov 2024·Environmental Health Perspectives

Organophosphorus Flame Retardants and Metabolic Disruption: An in Silico , in Vitro , and in Vivo Study Focusing on Adiponectin Receptors

Article

Author: Liu, Ying ; Xu, Mengting ; Le, Yifei ; Ma, Xiaochun ; Wang, Cui ; Wang, Wanyue ; Feng, Jiafan

BACKGROUNDEnvironmental chemical exposures have been associated with metabolic outcomes, and typically, their binding to nuclear hormone receptors is considered the molecular initiating event (MIE) for a number of outcomes. However, more studies are needed to understand the influence of such exposures on cell membrane-bound adiponectin receptors (AdipoRs), which are critical metabolic regulators.OBJECTIVEWe aimed to clarify the potential interactions between AdipoRs and environmental chemicals, specifically organophosphorus flame retardants (OPFRs), and the resultant effects.METHODSEmploying in silico simulation, cell thermal shift, and noncompetitive binding assays, we screened eight OPFRs for interactions with AdipoR1 and AdipoR2. We tested two key events underlying AdipoR modulation upon OPFR exposure in a liver cell model. The Toxicological Prioritization Index (ToxPi)scoring scheme was used to rank OPFRs according to their potential to disrupt AdipoR-associated metabolism. We further examined the inhibitory effect of OPFRs on AdipoR signaling activation in mouse models.RESULTSAnalyses identified pi-pi stacking and pi-sulfur interactions between the aryl-OPFRs 2-ethylhexyl diphenyl phosphate (EHDPP), triphenyl phosphate (TPhP), and tricresyl phosphate (TCP) and the transmembrane cavities of AdipoR1 and AdipoR2. Cell thermal shift assays showed a __-mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"-__>3°C rightward shift in the AdipoR proteins' melting curves upon exposure to these three compounds. Although the binding sites differed from adiponectin, results suggest that aryl-OPFRs noncompetitively inhibited the binding of the endogenous peptide ligand ADP355 to the receptors. Analyses of key events underlying AdipoR modulation revealed that glucose uptake was notably lower, whereas lipid content was higher in cells exposed to aryl-OPFRs. EHDPP, TCP, and TPhP were ranked as the top three disruptors according to the ToxPi scores. A noncompetitive binding between these aryl-OPFRs and AdipoRs was also observed in wild-type (WT) mice. In db/db mice, the finding of lower blood glucose levels after ADP355 injection was diminished in the presence of a typical aryl-OPFR (TCP). WT mice exposed to TCP demonstrated lower AdipoR1 signaling, which was marked by lower phosphorylated AMP-activated protein kinase (pAMPK) and a higher expression of gluconeogenesis-related genes. Moreover, WT mice exposed to ADP355 demonstrated higher levels of pAMPK protein and peroxisome proliferator-activated receptor-__-mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"-__α messenger RNA. This was accompanied by higher glucose disposal and by lower levels of long-chain fatty acids and hepatic triglycerides; these metabolic improvements were negated upon TCP co-treatment.CONCLUSIONSIn silico, in vitro, and in vivo assays suggest that aryl-OPFRs act as noncompetitive inhibitors of AdipoRs, preventing their activation by adiponectin, and thus function as antagonists to these receptors. Our study describes a novel MIE for chemical-induced metabolic disturbances and highlights a new pathway for environmental impact on metabolic health. https://doi.org/10.1289/EHP14634.

01 Oct 2024·iScience

Development of a non-invasive bioassay for adiponectin target engagement in mice

Article

Author: Abdul-Sater, Ali A ; Tang, Jialing ; Hsu, Henry H ; Abdul-Sater, Ali A. ; Hsu, Henry H. ; Sweeney, Gary ; Lei, Yubin ; Pignalosa, Angelica

Adiponectin-based therapeutic strategies are promising for managing metabolic diseases and reducing inflammation, prompting the development of adiponectin receptor agonists. However, monitoring their pharmacodynamic actions in clinical applications is challenging. This study aimed to identify peripheral biomarkers to monitor adiponectin actions using ALY688, an adiponectin receptor agonist peptide. RNA sequencing analysis of whole blood identified a cluster of genes that were significantly increased in the ALY688-treated group compared to the control. This gene cluster was validated by qPCR and further confirmed in human peripheral blood mononuclear cells treated with ALY688 ex vivo. We also confirmed a functional outcome of ALY688 action in mice as our study also demonstrated the anti-inflammatory effect of ALY688 in a sublethal LPS mouse model. In summary, a newly identified gene cluster signature is suitable for assessing the pharmacodynamic action of adiponectin or its mimetics in blood samples.

01 Jun 2024·Clinical and Translational Science

The adiponectin‐derived peptide ALY688 protects against the development of metabolic dysfunction‐associated steatohepatitis

Article

Author: Sung, Hye Kyoung ; Pignalosa, Angelica ; Wang, Qin ; Huang, Zhe ; Hsu, Henry H. ; He, Shiyu ; Sweeney, Gary ; Xu, Aimin ; Jin, Leigang ; Wu, Xuerui ; Crawford, Kathryn ; Yan, Xingqun

AbstractMetabolic dysfunction‐associated steatohepatitis (MASH) is the severe form of non‐alcoholic fatty liver disease which has a high potential to progress to cirrhosis and hepatocellular carcinoma, yet adequate effective therapies are lacking. Hypoadiponectinemia is causally involved in the pathogenesis of MASH. This study investigated the pharmacological effects of adiponectin replacement therapy with the adiponectin‐derived peptide ALY688 (ALY688‐SR) in a mouse model of MASH. Human induced pluripotent stem (iPS) cell‐derived hepatocytes were used to test cytotoxicity and signaling of unmodified ALY688 in vitro. High‐fat diet with low methionine and no added choline (CDAHF) was used to induce MASH and test the effects of ALY688‐SR in vivo. Histological MASH activity score (NAS) and fibrosis score were determined to assess the effect of ALY688‐SR. Transcriptional characterization of mice through RNA sequencing was performed to indicate potential molecular mechanisms involved. In cultured hepatocytes, ALY688 efficiently induced adiponectin‐like signaling, including the AMP‐activated protein kinase and p38 mitogen‐activated protein kinase pathways, and did not elicit cytotoxicity. Administration of ALY688‐SR in mice did not influence body weight but significantly ameliorated CDAHF‐induced hepatic steatosis, inflammation, and fibrosis, therefore effectively preventing the development and progression of MASH. Mechanistically, ALY688‐SR treatment markedly induced hepatic expression of genes involved in fatty acid oxidation, whereas it significantly suppressed the expression of pro‐inflammatory and pro‐fibrotic genes as demonstrated by transcriptomic analysis. ALY688‐SR may represent an effective approach in MASH treatment. Its mode of action involves inhibition of hepatic steatosis, inflammation, and fibrosis, possibly via canonical adiponectin‐mediated signaling.

News (Medical) associated with ALY-688

23 May 2023

·www.prnewswire.com

DelveInsight Evaluates a Robust Dry Eye Disease Clinical Trial Pipeline as 60+ Influential Pharma Players to Set Foot in the Domain

The prevalence of dry eye disease has been rising over the past few years, which prompts the growing demand for treatment options. The increasing prevalence of dry eye disease and the growing research and development activities to develop novel therapies to treat dry eye disease to drive the market. The companies developing the potential therapies in the last stage of development include Aldeyra Therapeutics, RegeneRx Biopharmaceuticals, Mitotech, and several others. LAS VEGAS, May 23, 2023 /PRNewswire/ -- DelveInsight's ' Dry Eye Disease Pipeline Insight – 2023 ' report provides comprehensive global coverage of pipeline dry eye disease therapies in various stages of clinical development, major pharmaceutical companies working to advance the pipeline space, and the future growth potential of the dry eye disease pipeline domain. Key Takeaways from the Dry Eye Disease Pipeline Report DelveInsight's dry eye disease pipeline report depicts a robust space with 50+ active players working to develop 60+ pipeline therapies for dry eye disease treatment. Key dry eye disease companies such as TearSolutions, Novaliq, HanAll Biopharma, Aldeyra Therapeutics, RegeneRx Biopharmaceuticals, Mitotech, Aerie Pharmaceuticals, Azura Ophthalmics, Stuart Therapeutics, Surface Ophthalmics, Glaukos Corporation, BRIM Biotechnology Inc., Dompé Farmaceutici S.p.A, Okyo Pharma Ltd, AxeroVision, Inc., Palatin Technologies, Seikagaku Corporation, Invirsa, Inc., Allysta Pharmaceutical, Taejoon Pharmaceutical Co., Ltd., Ocular Therapeutix, Inc., Dreamhawk Vision Biotech, Inc., Yuyu Pharma, Inc., Novartis Pharmaceuticals, VivaVision Biotech, Inc, Huons Co., Ltd., and others are evaluating new dry eye disease drugs to improve the treatment landscape. Promising dry eye disease pipeline therapies in various stages of development include Reproxalap, Timbetasin, Visomitin, HL036, CyclASol, Lacripep, AR15512, AZR MD 001, ST-100, SURF-100, SURF-200, GLK-301, BRM421, Oxervate, OK-101, AXR 159, AXR 270, PL9643, SI-614, INV-102, ALY688, TJO-083, OTX-CSI, OTX-DED, SHJ002, YP-P10, ECF843, VVN001, HU007 and others. In March 2023, Selagine, Inc., a spin-out company from the University of Illinois at Chicago (UIC), announced that it has entered into a research, development, and sublicense agreement with Grifols (Nasdaq: GRFS), a global leader in plasma-derived medicines, for the development and commercialization of immunoglobulin eye drops for dry eye disease.Under the agreement, Selagine will receive an upfront payment and annual collaboration fee. In addition, Grifols has committed to fund the development of immunoglobulin eye drops through FDA approval, which will be managed collaboratively by Grifols and Selagine, including the clinical, manufacturing and regulatory activities required for FDA approval for dry eye disease indication. In February 2023, Aldeyra Therapeutics, Inc. announced that the U.S. Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for topical ocular reproxalap, a first-in-class investigational new drug candidate, for the treatment of the signs and symptoms of dry eye disease. The FDA assigned a Prescription Drug User Fee Act (PDUFA) date of November 23, 2023. The FDA noted that no potential filing review issues have been identified, and that an advisory committee meeting is not currently planned. In February 2023, Novaliq, announced its plans for filing a Marketing Authorisation Application (MAA) for CyclASol® (ciclosporin ophthalmic solution), a first-of-its-kind anti-inflammatory product for the treatment of dry eye disease (DED) in the European Union. The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) determined that CyclASol® is eligible to be reviewed in a centralized procedure to receive a Union Marketing Authorisation for the European Economic Area (EEA). In January 2023, Bausch + Lomb Corporation and Novaliq GmbH, announced that Ophthalmology, the peer-reviewed journal of the American Academy of Ophthalmology, has published results from the pivotal Phase 3 trial GOBI, which is one of two pivotal Phase 3 trials for NOV03 (perfluorohexyloctane). NOV03 is being investigated to treat the signs and symptoms of dry eye disease (DED) associated with Meibomian gland dysfunction (MGD).In the study, NOV03 was well tolerated with few subjects experiencing ocular adverse events (AEs) (9.6% NOV03 group, 7.5% control group) or treatment-related ocular AEs (6.3% NOV03 group, 3.1% control group). In August 2022, Alcon and Aerie Pharmaceuticals, Inc. announced the companies have entered into a definitive merger agreement through which Alcon acquired Aerie. The transaction affirmed Alcon's commitment to the ophthalmic pharmaceutical space and is expected to add broader pharmaceutical R&D capabilities to Alcon's existing commercial expertise, maximizing the value of its diversified portfolio. Through the transaction, Alcon added the commercial products Rocklatan® (netarsudil and latanoprost ophthalmic solution) 0.02%/0.005% and Rhopressa® (netarsudil ophthalmic solution) 0.02%, as well as AR-15512, a Phase 3 product candidate for dry eye disease, and a pipeline of several clinical and preclinical ophthalmic pharmaceutical product candidates. In May 2022, Yuyu Pharmaceutical presented a poster study for YP-P10, its new dry eye syndrome treatment, during the 2022 ARVO (Association for Research in Vision and Ophthalmology) conference. YP-P10 is a new biopharmaceutical using synthetic peptides, aiming to relieve signs and symptoms of dry eye syndrome caused by inflammation by administering the treatment twice a day. According to preclinical trial results unveiled at the conference, Yuyu confirmed that the candidate had an excellent anti-inflammatory mechanism and corneal epithelial cell healing effect compared to existing drugs. Request a sample and discover the recent advances in dry eye disease drug treatment @ Dry Eye Disease Pipeline Report The dry eye disease pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage dry eye disease drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the dry eye disease clinical trial landscape. Dry Eye Disease Overview Dry eye disease is characterized as a multifactorial disease of the tears and ocular surface that causes symptoms such as pain, visual disruption, and tear film instability, as well as potential ocular surface damage. It is accompanied by increased tear osmolarity and transient ocular surface irritation. When tear production and drainage are out of balance, dry eyes can result. People with dry eyes either do not produce enough tears or have poor-quality tears. Dry eyes can occur for various reasons, including age, gender, drugs, and medical disorders. Dry eye disease symptoms include redness, stinging, itching, or burning sensations, light sensitivity, watery eyes, stringy mucus near the eye, and blurred vision. A thorough eye examination can detect dry eyes. Dry eye disease treatments seek to restore or maintain the usual number of tears in the eye in order to reduce dryness and associated discomfort and to maintain eye health. The basic approaches used to manage and treat dry eyes include adding tears with over-the-counter artificial tear solutions, conserving tears, boosting tear production, and treating the inflammation of the eyelids or eye surface that contributes to dry eyes. Find out more about drugs for dry eye disease @ New Dry Eye Disease Drugs A snapshot of the Dry Eye Disease Pipeline Drugs mentioned in the report: Learn more about the emerging dry eye disease pipeline therapies @ Dry Eye Disease Clinical Trials Dry Eye Disease Therapeutics Assessment The dry eye disease pipeline report proffers an integral view of dry eye disease emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Dry Eye Disease Pipeline Report Coverage: Global Dry Eye Disease Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Dry Eye Disease Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Dry Eye Disease Therapeutics Assessment By Route of Administration: Intra-articular, Intraocular, Intrathecal, Intravenous, Ophthalmic, Oral, Parenteral, Subcutaneous, Topical, Transdermal Dry Eye Disease Therapeutics Assessment By Molecule Type: Oligonucleotide, Peptide, Small molecule Dry Eye Disease Therapeutics Assessment By Mechanism of Action: Malondialdehyde inhibitors, Actin modulators, Amyloid inhibitors, Angiogenesis inducing agents, Apoptosis inhibitors, Cell movement activators, Collagen stimulants, Heat-shock protein modulators, MicroRNA modulators, Nerve growth factor stimulants, NF-kappa B inhibitors, Stem cell stimulants, Antioxidants, Electron transport chain complex protein modulators, Lipid modulators, Tumour necrosis factor alpha inhibitors, Eye protein modulators, TRPM8 protein stimulants, Glucocorticoid receptor agonists, Inosine monophosphate dehydrogenase inhibitors, Muscarinic receptor agonists Key Dry Eye Disease Companies: TearSolutions, Novaliq, HanAll Biopharma, Aldeyra Therapeutics, RegeneRx Biopharmaceuticals, Mitotech, Aerie Pharmaceuticals, Azura Ophthalmics, Stuart Therapeutics, Surface Ophthalmics, Glaukos Corporation, BRIM Biotechnology Inc., Dompé Farmaceutici S.p.A, Okyo Pharma Ltd, AxeroVision, Inc., Palatin Technologies, Seikagaku Corporation, Invirsa, Inc., Allysta Pharmaceutical, Taejoon Pharmaceutical Co., Ltd., Ocular Therapeutix, Inc., Dreamhawk Vision Biotech, Inc., Yuyu Pharma, Inc., Novartis Pharmaceuticals, VivaVision Biotech, Inc, Huons Co., Ltd., and others. Key Dry Eye Disease Pipeline Therapies: Reproxalap, Timbetasin, Visomitin, HL036, CyclASol, Lacripep, AR15512, AZR MD 001, ST-100, SURF-100, SURF-200, GLK-301, BRM421, Oxervate, OK-101, AXR 159, AXR 270, PL9643, SI-614, INV-102, ALY688, TJO-083, OTX-CSI, OTX-DED, SHJ002, YP-P10, ECF843, VVN001, HU007, and others. Dive deep into rich insights for new drugs for dry eye disease treatment; visit @ Dry Eye Disease Medications Table of Contents For further information on the dry eye disease pipeline therapeutics, reach out @ Dry Eye Disease Drug Treatment Related Reports Dry Eye Disease Market Dry Eye Disease Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key dry eye disease companies, including Oyster Point Pharma, Aerie Pharmaceuticals, Azura Ophthalmics, Stuart Therapeutics, Surface Ophthalmics, Glaukos Corporation, among others. Dry Eye Disease Epidemiology Forecast Dry Eye Disease Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, and dry eye disease epidemiology trends. Mild Dry Eye Market Mild Dry Eye Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key mild dry eye companies, including Allergan Plc., Novartis AG., Otsuka Pharmaceutical Co. Ltd., Santen Pharmaceutical Co. Ltd., among others. Moderate Dry Eye Market Moderate Dry Eye Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key moderate dry eye companies, including Santen Pharmaceutical Co. Ltd., OASIS Medical, Alcon Inc., Bausch Health Companies Inc., AbbVie Inc., among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +1(919)321-6187 Logo: SOURCE DelveInsight Business Research, LLP

Phase 3Clinical ResultAcquisition

100 Deals associated with ALY-688

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Dry Eye Syndromes	Phase 3	US	Allysta Pharmaceuticals, Inc.Startup	19 May 2021
Muscular Dystrophy, Duchenne	Preclinical	US	Allysta Pharmaceuticals, Inc.Startup	19 Feb 2024
Primary Biliary Cholangitis	Preclinical	US	Allysta Pharmaceuticals, Inc.Startup	19 Feb 2024
Pulmonary Fibrosis	Preclinical	US	Allysta Pharmaceuticals, Inc.Startup	19 Feb 2024
Scleroderma, Systemic	Preclinical	US	Allysta Pharmaceuticals, Inc.Startup	19 Feb 2024
Obesity	Preclinical	AU	Allysta Pharmaceuticals, Inc.Startup	19 May 2021

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ARVO2023	Phase 1/2	Dry Eye Syndromes	138	ALY688 Ophthalmic Solution 0.4%	(gbbskepkol) = zpmuivzols eviouizcwg (jvqrovympw, 2.34) View more	-	23 Apr 2023
ARVO2023	Phase 1/2	Dry Eye Syndromes	138	Vehicle	(gbbskepkol) = knavlfewqe eviouizcwg (jvqrovympw, 2.25) View more	-	23 Apr 2023
NCT04201574 (Corporate Publications) Manual	Phase 1/2	Dry Eye Syndromes	138	ALY 688	(jgcupqtxyw) = with no adverse systemic effects. neemdgjhww (mrpioqqaqc )	Positive	01 Dec 2022

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