AZD1656 / AstraZeneca, Conduit Pharmaceuticals - LARVOL DELTA

Conduit Pharmaceuticals Receives Further Patent Approval For Its Lead Asset Targeting Autoimmune Diseases (GlobeNewswire) - "Conduit Pharmaceuticals Inc...announces that the Korean Intellectual Property Office (KIPO) has granted the composition of matter patent for its lead asset, AZD1656, a Glucokinase Activator targeting autoimmune diseases. This approval follows recent grants in the U.S., Japan and Australia and further strengthens Conduit's global intellectual property position as it advances out-licensing discussions. Notably, South Korea is often commercially partnered with Japan in licensing and distribution arrangements by major Western pharmaceutical companies, making this an important strategic milestone in expanding Conduit’s reach across a highly valuable Asia-Pacific pharmaceutical region."

Patent • Immunology

Immunomodulation by AZD1656 reverses cardiac dysfunction, metabolic remodelling and reduces infarct size in type 2 diabetic cardiomyopathy. (PubMed, bioRxiv) - "20-week db/db mice displaying the features of human dbCM (obesity, hyperglycaemia and diastolic dysfunction) treated for six weeks with AZD showed improved metabolic remodelling, attenuated diastolic dysfunction, reduced infarct size and improved functional post-ischemic recovery compared to untreated dbCM, alongside an improved cardiac immunophenotype, including reduced T cell-mediated fibrosis and B cell infiltration. Therefore, targeting of immunometabolism may offer a new therapeutic approach to treat cardiac dysfunction and metabolic dysregulation and reduce infarct size in dbCM."

Journal • Cardiomyopathy • Cardiovascular • Diabetes • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Metabolic Disorders • Novel Coronavirus Disease • Obesity • Type 2 Diabetes Mellitus

Conduit Pharmaceuticals Expands Partnership with Sarborg Limited to Leverage Machine Learning Data Analysis for Pipeline Optimization (GlobeNewswire) - "Conduit Pharmaceuticals Inc...announces that it has entered into an additional license and use agreement (the 'Additional Agreement') with Sarborg Limited ('Sarborg') to expand the scope of work on Conduit’s acquired AstraZeneca assets, including AZD1656, AZD5658, and AZD5904...Under the agreement, Sarborg will apply its proprietary machine learning algorithms to conduct an in-depth analysis of Conduit’s clinical and safety data, with the goal of uncovering missed insights, identifying potential drug repurposing opportunities, and highlighting gaps in existing datasets. A key focus will be the re-evaluation of historical clinical trial data, including endpoints, to determine whether specific patient subgroups may have demonstrated therapeutic benefits, findings that could refine Conduit’s future clinical development strategy."

Commercial • Immunology • Lupus

Conduit Pharmaceuticals Receives U.S. Patent Approval For Its Lead Asset Targeting Autoimmune Diseases (GlobeNewswire) - "Conduit Pharmaceuticals...announces that the United States Patent and Trademark Office (USPTO) has granted the composition of matter patent for its lead asset, AZD1656, a Glucokinase Activator targeting autoimmune diseases, including Lupus and ANCA Vasculitis. With this critical composition of matter patent protection now secured, the Company is strategically positioned to advance AZD1656 into clinical development, with clinical trial plans now in final stages of preparation....Composition of matter patents, classified as 'drug substance' patents in the U.S. FDA’s Orange Book, represent the gold standard in pharmaceutical intellectual property, providing strong market exclusivity and robust protection against generic competition."

Patent • ANCA Vasculitis • Lupus

Conduit Pharmaceuticals Provides Research and Development Update on Progress for Pipeline Assets AZD1656, AZD5658... (GlobeNewswire) - "Conduit Pharmaceuticals Inc...today provides an R&D update on the development progress of pipeline assets AZD1656, AZD5658...Conduit has partnered with Charles River Laboratories Inc. to conduct preclinical studies evaluating its glucokinase inhibitors towards applications in autoimmune diseases, with an initial focus on lupus...This study is expected to generate critical data on the therapeutic potential, informing future clinical development plans with results anticipated in Q2 2025...In parallel, Conduit continues to optimize the protocol for the design of its Phase II clinical trial for AZD1656...Recent milestones include the grant of a composition-of-matter patent for the AZD1656 Cocrystals by the Japan Patent Office (JPO) and IP Australia...In addition, Conduit is actively working to develop new solid forms of its key assets, including AZD1656...AZD5658."

Clinical protocol • Patent • Pipeline update • Preclinical • Immunology • Lupus • Systemic Lupus Erythematosus

Conduit Pharmaceuticals Partners with Charles River in Clinically Relevant Systemic Lupus Erythematosus Model (GlobeNewswire) - "Conduit Pharmaceuticals Inc...is pleased to announce an agreement with Charles River Laboratories Inc...to evaluate AZD1656 (and its derivatives) in a clinically relevant Systemic Lupus Erythematosus model. This collaboration highlights Conduit’s focus on generating high-quality preclinical data to optimize the development pathway for its clinical program in auto-immune and position itself for success in its upcoming Phase II clinical trials. Conduit will leverage Charles River’s expertise in immunology and preclinical research to refine study parameters and generate robust data to evaluate the efficacy of its lead compound. By conducting this comprehensive study, Conduit aims to enhance the predictability of clinical outcomes, increase the efficiency of its planned Phase II trials, and ultimately improve the likelihood of success for AZD1656 as a potential treatment for autoimmune disorders."

Commercial • Systemic Lupus Erythematosus

Evaluating the Overall Safety of Glucokinase Activators in Patients with Type 2 Diabetes Mellitus. (PubMed, Diabetes Metab Syndr Obes) - "Among the 17 RCTs, dorzagliatin, AZD1656 and MK-0941 in three trials (1,541 patients), five trials (885 patients), and three trials (798 patients), respectively. The results of our meta-analysis indicated that GKAs were associated with a higher risk of any AEs, mild AEs, hyperlipidemia, and hyperuricemia. Further subgroup analyses revealed that the increased occurrence of hyperlipidemia, and hyperuricemia mainly originated from dorzagliatin treatment."

Journal • Review • Diabetes • Dyslipidemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Compromised chronic efficacy of a glucokinase activator AZD1656 in mouse models for common human GCKR variants. (PubMed, Biochem Pharmacol) - "Chronic treatment with AZD1656 in the Gckr-del/wt mouse was associated with raised liver triglyceride and hepatocyte microvesicular steatosis. The results show that in mouse models of liver GKRP deficiency in conjunction with functional liver glucokinase excess as occurs in association with common human GCKR variants, GKRP-deficiency predisposes to declining efficacy of the GKA in lowering blood glucose and to GKA induced elevation in liver lipids."

Journal • Preclinical • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Conduit Pharmaceuticals Enters into Exclusive License Agreement with AstraZeneca for Multiple Assets to Advance Potential First-in-Class Treatments (GlobeNewswire) - "Conduit Pharmaceuticals...today announced that the Company has entered into an agreement with AstraZeneca to exclusively license rights to develop AZD1656 and AZD5658, both HK-4 glucokinase activators, and AZD5904, a myeloperoxidase inhibitor (MPO). AstraZeneca had progressed AZD1656 and AZD5904 through Phase 1 clinical trials....Conduit initially intends to conduct Phase II clinical trials on clinical candidates AZD1656 and AZD5658 in 2024 for applications in autoimmune disorders...Under the terms of the License Agreement, AstraZeneca will grant Conduit an exclusive license to both AZD1656 and AZD5658 for all human indications..."

Licensing / partnership • New P2 trial • Immunology

ADOPTION: AZD1656 in Transplantation With Diabetes tO PromoTe Immune TOleraNce (clinicaltrials.gov) - P2 | N=26 | Completed | Sponsor: Queen Mary University of London | N=50 ➔ 26 | Active, not recruiting ➔ Completed

Enrollment change • Trial completion • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • Transplantation • Type 2 Diabetes Mellitus

ADOPTION: AZD1656 in Transplantation With Diabetes tO PromoTe Immune TOleraNce (clinicaltrials.gov) - P2 | N=50 | Active, not recruiting | Sponsor: Queen Mary University of London | Trial completion date: May 2023 ➔ Aug 2023

Trial completion date • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • Transplantation • Type 2 Diabetes Mellitus

ADOPTION: AZD1656 in Transplantation With Diabetes tO PromoTe Immune TOleraNce (clinicaltrials.gov) - P2 | N=50 | Active, not recruiting | Sponsor: Queen Mary University of London | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2022 ➔ May 2023 | Trial primary completion date: Sep 2022 ➔ Mar 2023

Enrollment closed • Trial completion date • Trial primary completion date • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • Transplantation • Type 2 Diabetes Mellitus

ADOPTION Study Protocol: AZD1656 in Transplantation With Diabetes to Promote Immune Tolerance (KIDNEY WEEK 2022) - "We hope to demonstrate that AZD1656 increases Treg localisation to the renal transplant and provides an effective and safe adjunct for the management of diabetes in the early post-transplant period. A positive signal generated by this pilot study would provide future opportunities for further study and we look forward to sharing our results with the ASN in the near future."

Clinical • Chronic Kidney Disease • Diabetes • Immune Modulation • Inflammation • Metabolic Disorders • Nephrology • Transplantation • Type 2 Diabetes Mellitus

Chronotherapy with a glucokinase activator profoundly improves metabolism in obese Zucker rats. (PubMed, Sci Transl Med) - "In conclusion, intermittent AZD1656 treatment timed to feeding periods promotes glucose disposal when needed the most, restores metabolic flexibility and hepatic insulin sensitivity, and thereby avoids hepatic steatosis. Thus, chronotherapeutic approaches may benefit the development of GKAs and other drugs acting on metabolic targets."

Journal • Preclinical • Diabetes • Dyslipidemia • Hypoglycemia • Immunology • Inflammation • Obesity

A randomised, double-blind, placebo-controlled, multicentre clinical trial of AZD1656 in diabetic patients hospitalised with COVID-19: The ARCADIA Trial - implications for therapeutic immune modulation. (PubMed, EClinicalMedicine) - P2 | "Phase 2 trials of this size carry the risk of false positive results and confirmation of these results in a larger clinical trial is now required. UK Research and Innovation (UKRI) 'Innovate UK' programme and Excalibur Medicines Ltd."

Clinical • Journal • Diabetes • Immune Modulation • Immunology • Infectious Disease • Inflammation • Metabolic Disorders • Novel Coronavirus Disease • Respiratory Diseases

Development of the glucokinase activator AZD1656: Part 2 (ACS-Fall 2022) - "Downstream challenges included an amidation reaction with a pyrazine coupling partner made using a Curtius rearrangement performed in batch mode, and the development of crystallization conditions that allowed the reproducible isolation of a slow-growing polymorph of the API. The processes developed were tested as part of a 500kg manufacture of AZD1656."

Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Chronotherapy with the Glucokinase Activator AZD1656 Greatly Affects Its Ability to Improve Metabolism in Obese Zucker Rats (ADA 2022) - "In conclusion, intermittent AZD1656 dosing timed to feeding periods promotes glucose disposal when needed the most, while the daily drug holiday allows for maintained metabolic flexibility and avoids hepatic steatosis. Chronotherapeutic approaches should be considered for the development of GKAs and other drugs acting on metabolic targets."

Preclinical • Diabetes • Hypoglycemia • Metabolic Disorders • Obesity

ADOPTION: AZD1656 in Transplantation With Diabetes tO PromoTe Immune TOleraNce (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Queen Mary University of London

New P2 trial • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • Transplantation • Type 2 Diabetes Mellitus

Glucokinase as an emerging anti-diabetes target and recent progress in the development of its agonists. (PubMed, J Enzyme Inhib Med Chem) - "Among these agents, dorzagliatin is currently being investigated in phase III clinical trials, while PB-201 and AZD-1656 have reached phase II clinical trials. This article describes the mechanism of action of GK in diabetes and of action of GKA at the protein level, and provides a review of the research, trends, and prospects regarding the use of GKA in this setting."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

ARCADIA study protocol: a phase II, randomised, double-blind, placebo-controlled clinical trial to assess the safety and efficacy of AZD1656 in patients with diabetes hospitalised with suspected or confirmed COVID-19. (PubMed, BMJ Open) - P2 | "Anonymised data will be stored in an ISO27001 certificated data warehouse. EudraCT 2020-002211-21, NCT04516759."

Clinical • Journal • P2 data • Diabetes • Immunology • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease • Respiratory Diseases • Type 2 Diabetes Mellitus

ARCADIA: AZD1656 in Diabetic Patients Hospitalised With Suspected or Confirmed COVID-19 (clinicaltrials.gov) - P2; N=156; Completed; Sponsor: St George Street Capital; Active, not recruiting ➔ Completed

Clinical • Trial completion • Diabetes • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease

ARCADIA: AZD1656 in Diabetic Patients Hospitalised With Suspected or Confirmed COVID-19 (clinicaltrials.gov) - P2; N=156; Active, not recruiting; Sponsor: St George Street Capital; Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease

ARCADIA: AZD1656 in Diabetic Patients Hospitalised With Suspected or Confirmed COVID-19 (clinicaltrials.gov) - P2; N=150; Recruiting; Sponsor: St George Street Capital; Trial completion date: Dec 2020 ➔ Mar 2021; Trial primary completion date: Dec 2020 ➔ Mar 2021

Clinical • Trial completion date • Trial primary completion date • Diabetes • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease

ARCADIA: AZD1656 in Diabetic Patients Hospitalised With Suspected or Confirmed COVID-19 (clinicaltrials.gov) - P2; N=150; Recruiting; Sponsor: St George Street Capital; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Diabetes • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease

London hospitals launch trial of drug that could reduce coronavirus risk in diabetics (London Evening Standard) - "London hospitals are launching trials of a drug that doctors hope will reduce the risk of people with diabetes becoming seriously ill or dying from coronavirus....Medics at the Royal London and Whipps Cross hospitals are leading a national trial that will offer people with type 1 or 2 diabetes who are admitted for treatment for covid an additional therapy....About 150 patients in 15 UK hospitals will be involved in the 'Arcadia' trials over the next four months."

Cytokine storm • New P2 trial • Diabetes • Infectious Disease • Novel Coronavirus Disease