17β-HSD13

CAMBRIDGE, England--( BUSINESS WIRE )--CN Bio, a leading Organ-on-a-Chip (OOC) company that designs and manufactures single-and multi-organ microphysiological systems (MPS), today announced its PhysioMimix ® assay for Non-alcoholic steatohepatitis (NASH) was important for confirmation of efficacy for INI-822 from Inipharm, a biopharmaceutical company focused on discovering and developing therapies for severe liver diseases. The use of in vitro OOC for early evidence of efficacy for INI-822 demonstrates the transformative potential of these models to provide human-relevant data within preclinical programmes. Inipharm has initiated Phase 1 dosing of its lead candidate 1 , INI-822. INI-822 is a small-molecule inhibitor for HSD17B13, a gene implicated in NASH. Loss-of-function variants of this gene are known to be associated with reduced incidence risk and severity of multiple liver diseases. As part of the recent regulatory submission, CN Bio’s Contract Research Services team utilised the Company’s PhysioMimix OOC Systems and NASH ‘in-a-box' (NIAB) kit to generate critical data to determine compound efficacy. Despite research efforts to combat the growing prevalence of NASH, there are currently no regulatory approved therapeutics due to the inability of traditional in vivo approaches to accurately predict the human response to this complex metabolic disease. In conjunction with the PhysioMimix OOC, CN Bio’s ‘in-a-box’ range aims to fast-track the incorporation of MPS into drug discovery workflows by providing a straightforward and quick route to recreating the Company’s industry-proven models and assays. The NIAB kit was launched to support the urgent development of NASH therapeutics, providing physiologically relevant insights into the mechanism of disease, human drug efficacy and potential treatment regimens. The assay addresses the human-relevance limitations of existing approaches, bridging the gap between human 2D cell culture and expensive animal models, which are ineffective in mimicking the full disease spectrum. Dr. Tomasz Kostrzewski, Chief Scientific Officer, said: “Inipharm’s progression to clinic is absolutely fantastic news and holds immense potential for patients worldwide. We are thrilled that our PhysioMimix system was able to provide physiologically relevant data to support the regulatory submission, becoming the first OOC provider whose data is supporting a drug to enter the clinic for a widespread metabolic, fibrotic liver disease.” He added: “Despite its prevalence, development of NASH treatments has been constrained for a long time due to a lack of clinical translatability during preclinical research. Inipharm’s recent submission has shown that OOC technology provides a clear route to overcoming this problem by enabling therapeutic developers to de-risk and avoid potential cross-species differences.” CN Bio’s predictive, human, in vitro NASH model is available to customers via the Company’s Contract Research Services, or via the off-the-shelf NIAB kit, enabling users to incorporate the PhysioMimix NASH model into their own workflows. For more information, visit: https://cn-bio.com/ Inipharm Initiates Dosing in Phase 1 Study of Its Small Molecule Inhibitor of HSD17B13: https://www.businesswire.com/news/home/20231130655005/en/

BELLEVUE, Wash. & SAN DIEGO--(BUSINESS WIRE)-- Inipharm, a biopharmaceutical company focused on discovering and developing therapies for severe liver diseases, today announced that it has begun dosing in a Phase 1 study of INI-822, its orally-delivered small molecule inhibitor of HSD17B13. INI-822, believed to be the first small molecule inhibitor of HSD17B13 to advance to clinical development, is under development for fibrotic liver diseases, including non-alcoholic steatohepatitis (NASH). “Multiple human genetic validation studies demonstrate that inactive forms of HSD17B13 protect against the progression to more advanced stages of several liver diseases including NASH,” said Chuhan Chung, M.D., chief medical officer of Inipharm. “Other development approaches are focused on RNA knockdown of HSD17B13, but those must be delivered via injection. INI-822, if successful in clinical studies, would offer an oral option that may be more suitable for treating a chronic disease like NASH.” The randomized, double-blind, placebo-controlled Phase 1 study will enroll 96 participants in three parts. Parts A and B will enroll approximately 72 healthy volunteers, and Part C will enroll 24 participants with NASH or presumed NASH. The study is designed to assess safety and tolerability and pharmacokinetics of INI-822, as well as biomarkers of target engagement. In preclinical studies, INI-822 was shown to potently and selectively inhibit HSD17B13, and when dosed in animal models, demonstrated improvements in markers of liver homeostasis. These included a reduction in liver transaminases and specific bioactive lipids, and the enrichment of hepatic lipid species that were also identified in patients with the protective variant of HSD17B13. “HSD17B13 inhibition represents a genetically validated approach that may improve multiple aspects of liver injury, such as inflammation and fibrosis. This could be as standalone therapy or in combination with other therapies that reduce liver fat but may not directly address key features of liver injury,” added Chung. “I want to applaud the Inipharm team who has worked tirelessly to develop a small molecule that can inhibit HSD17B13,” said Brian Farmer, co-founder and chief executive officer of Inipharm. “This target presents significant challenges with respect to the development of a small molecule inhibitor. I am grateful for the dedication of our team, collaborators and investors. The start of clinical development for this program is a significant milestone for Inipharm.” About HSD17B13 and INI-822 Multiple human genetic association studies have confirmed that enzymatically inactive variants of the HSD17B13 protein are associated with a reduced risk of developing more advanced fibrotic disease in metabolic, alcoholic, and viral liver diseases. INI-822, a small molecule inhibitor of HSD17B13, is Inipharm’s first development candidate. About Inipharm Inipharm is a biopharmaceutical company focused on discovering and developing therapies for severe liver diseases. Inipharm’s lead programs are focused on the highly validated genetic target, HSD17B13. Extensive, consistent evidence that genetic variants in expression of HSD17B13 are associated with significantly lower rates and severity of multiple liver diseases. Building on these novel insights into the biologic activity of HSD17B13, Inipharm is advancing a pipeline of small-molecule therapies that target the activity of this protein.

LONDON, UK I October 31, 2023 I GSK plc (LSE/NYSE: GSK) and Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) today announced that they have reached an agreement with Janssen Pharmaceuticals, Inc. (Janssen), a Johnson & Johnson company, to transfer exclusive worldwide rights to further develop and commercialise JNJ-3989 to GSK. JNJ-3989 (formerly ARO-HBV) was initially in-licensed by Janssen from Arrowhead in 2018. JNJ-3989 is an investigational hepatitis B virus-targeted small interfering ribonucleic acid (siRNA) therapeutic that GSK intends to evaluate in a sequential regimen with bepirovirsen, GSK’s investigational antisense oligonucleotide, for the treatment of adult non-cirrhotic patients with chronic hepatitis B (CHB) on nucleos(t)ide analogue (NA) therapy. There is high unmet need in CHB with an estimated 300 million people living with the disease and a less than 3-7% functional cure rate with current treatment options. 1,2 Patients reach functional cure when the hepatitis B virus and viral proteins are at levels low enough to be undetectable in blood and can be controlled by the immune system without medication. Bepirovirsen is the only single agent in phase III development that has shown clinically meaningful functional cure response for patients with CHB receiving oral NAs, following positive results demonstrated in the B-Clear and B-Sure clinical trials. 3,4 B-Clear identified sub-groups of patients most likely to benefit from treatment with bepirovirsen, and also solidified bepirovirsen as a potential backbone therapy in future sequential regimens to pursue functional cure in additional patients with CHB. Tony Wood, Chief Scientific Officer, GSK, said: “We are excited to build on promising results already demonstrated with bepirovirsen to investigate a novel sequential regimen with JNJ-3989. We believe this approach could redefine the treatment paradigm for chronic hepatitis B by helping even more patients achieve functional cure.” Chris Anzalone, Ph.D., President and CEO of Arrowhead said : “GSK has a global reach, a clear commitment to help those living with chronic hepatitis B, and a promising strategy for clinical studies designed to improve functional cure rates. We have great confidence in the team at GSK and look forward to seeing this program progress towards the goal of potentially helping the millions of patients with chronic hepatitis B worldwide without adequate treatment options. We would also like to thank our colleagues at Janssen for the great progress they made with JNJ-3989, the investigational siRNA therapeutic that Arrowhead discovered and initially developed.” JNJ-3989 has the potential to move immediately into a phase II sequential regimen trial with bepirovirsen beginning in 2024, further strengthening GSK’s late-stage pipeline of specialty medicines. This transaction is aligned with GSK’s leadership in the treatment and prevention of infectious diseases and commitment to the development of oligonucleotide therapeutics. This transaction builds on GSK’s relationship with Arrowhead, following the 2021 exclusive license of GSK4532990 (ARO-HSD), an investigational oligonucleotide therapeutic targeting HSD17B13 as a potential treatment for patients with alcohol-related and nonalcohol related liver diseases. The exclusive license granted GSK rights to further develop and commercialise GSK4532990 outside of Greater China. Terms of the transaction Upon closing of the transaction, GSK will assume rights and obligations of the existing license agreement between Janssen and Arrowhead, including all remaining financial obligations owed to Arrowhead for JNJ-3989 under the original agreement. GSK will be responsible for upfront and potential milestone-based payments to both Janssen and Arrowhead totalling approximately $1 billion. Janssen will continue to be responsible for the ongoing clinical trials of JNJ-3989 at its expense and GSK will be solely responsible for all future development and commercialisation activities. Additionally, Arrowhead will receive tiered royalties on net sales pursuant to the original agreement. This transaction is subject to customary conditions, including applicable regulatory agency clearances under the Hart-Scott-Rodino Act in the US. About CHB Hepatitis B is a viral infection of the liver, caused by the hepatitis B virus, that can cause both acute and chronic liver disease. 5 Chronic hepatitis B (CHB) is a long-lasting infection and occurs when the body’s immune system is unable to fight off the virus and it persists in the blood and liver. 6 CHB is a major global health issue, affecting nearly 300 million people across the world, although only about 10% of these people have a diagnosis and only 5% receive treatment. 1 Even when treated, CHB can progress to liver complications including cirrhosis and liver cancer, which results in almost a million deaths per year. 1,6 About JNJ-3989 JNJ-3989 is a liver-targeted siRNA antiviral therapeutic for subcutaneous injection designed to treat chronic hepatitis B virus infection via a ribonucleic acid interference (RNAi) mechanism. About bepirovirsen (GSK3228836) Bepirovirsen is a triple-action investigational antisense oligonucleotide (ASO), currently being evaluated in the B-Well phase III clinical trial programme for the treatment of CHB. Bepirovirsen is designed to recognise and destroy the genetic components (i.e. RNA) of the hepatitis B virus that can lead to chronic disease, potentially allowing a person’s immune system to regain control. Bepirovirsen inhibits the replication of viral DNA in the body, suppresses the level of hepatitis B surface antigen (HBsAg) in the blood, and stimulates the immune system to increase the chances of a durable and sustained response. Bepirovirsen (previously known as ‘ISIS 505358 or IONIS-HBVRX’) was discovered by and jointly developed with Ionis Pharmaceuticals. Bepirovirsen is one of the ASO HBV programme assets in-licensed by GSK from Ionis Pharmaceuticals in August 2019. About Arrowhead Pharmaceuticals Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing. For more information, please visit www.arrowheadpharma.com , or follow us on Twitter @ArrowheadPharma . To be added to the Company's email list and receive news directly, please visit http://ir.arrowheadpharma.com/email-alerts . About GSK GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com. References SOURCE: GlaxoSmithKline