EPO receptor

Hitting targets embedded within the cell membrane has long been difficult for drug developers due to the membrane's challenging biochemical properties. Now, chemists have demonstrated new custom-designed proteins that can efficiently reach these 'intramembrane' targets. Hitting targets embedded within the cell membrane has long been difficult for drug developers due to the membrane's challenging biochemical properties. Now, Scripps Research chemists have demonstrated new custom-designed proteins that can efficiently reach these "intramembrane" targets. In their study, published March 13, 2024, in Nature Chemical Biology, the researchers used a unique computer-based approach to design novel proteins targeting the membrane-spanning region of the erythropoietin (EPO) receptor, which controls red blood cell production and can go awry in cancers. In addition to these new EPO-targeting molecules, the study yielded a general computational process, or "workflow," for streamlining the flexible custom design of proteins aimed at intramembrane targets. The researchers are now using their approach to develop potential new intramembrane-targeting treatments across a wide range of diseases. "This work opens up many new possibilities for the modulation of targets within the cell membrane, including for therapeutic applications and understanding signaling mechanisms across cell biology," says study co-corresponding author Marco Mravic, PhD, an assistant professor in the Department of Integrative Structural and Computational Biology at Scripps Research. The study's other co-corresponding authors were Daniel DiMaio, MD, PhD, of the Yale School of Medicine; and William DeGrado, PhD, of the University of California, San Francisco School of Pharmacy, where Mravic was previously a PhD student. "A major goal of synthetic biology is to design proteins with biological activity -- here, we report the design and testing of a small protein that specifically perturbs the activity of a much larger protein receptor involved in blood cell growth and differentiation," says DiMaio, who is a professor of Genetics and of Molecular Biophysics and Biochemistry, and deputy director of Yale Cancer Center. "We accomplished this by targeting the segment of the receptor that crosses the cell membrane. Because many cell proteins contain structurally conserved membrane-spanning segments, this general approach may be applicable to many other protein targets and provides a new tool to modulate the behavior of cells." Hitting intramembrane targets has long been an important goal in biomedicine since many proteins in cells -- especially receptor proteins -- have functionally important domains inside the membrane. Such proteins have prominent roles in almost every area of health and disease. Yet intramembrane targets are not ordinary targets. Cell membranes generally are made of two layers of tightly spaced, fat-related "lipid" molecules, which are water-repellent and have other unique and complex properties. This makes the intramembrane space a much harder target for drug designers, compared to the watery zones of cell surfaces or interiors. "There have been very few successful examples of drugs that target this space inside the membrane," Mravic says. Those few successes, which include treatments for low-blood-platelet disorders and cystic fibrosis, have come from blind screenings of large compound libraries or from close mimicry of proteins known to interact with partner proteins within the cell membrane. By contrast, Mravic and colleagues set out to design completely novel proteins -- small ones called peptides -- to hit intramembrane protein targets in new and diverse ways. To do that, they had to extend the frontier of computational methods, combining "data mining" of known protein-to-protein interactions in membranes with traditional physics-based predictions of protein interactions. Ultimately, Mravic and his colleagues designed the first proteins that bind the EPO receptor's membrane-spanning portion in a new way -- not seen in nature. The team showed that these proteins very specifically and potently block the receptor's function, in contrast to prior approaches. The results may be of most immediate interest to researchers seeking new ways to inhibit the EPO receptor, which is often abnormally activated by tumor cells to maintain their growth and survival. But for Mravic and his colleagues, the study above all represents a proof of principle of a new and more flexible approach to intramembrane targeting. "We intend to use this approach to target membrane proteins across multiple biological processes and disease areas, including cancers, immune disorders, and pain," Mravic says. He also expects the computational workflow he designed for the project to be a general accelerator of membrane-targeting drug design. "Before, the process basically involved two people in a dark room looking at a computer screen and saying, 'Yeah, I think this looks better than that,'" Mravic says. "Now, we've automated a lot of that molecule design process and decision making in the computer. Being more modular, flexible and streamlined allows the method to be more accessible for a broader range of scientists."

SEOUL, South Korea I October 23, 2023 I Genexine (KQ 095700, CEO Sungjune Hong), a publicly-listed clinical-staged Korean biopharmaceutical company committed to the discovery and development of novel biologics for the treatment of unmet medical needs, together with PT Kalbe Genexine Biologics (KGbio), a joint venture clinical-stage biotechnology company between Genexine and PT Kalbe Farma that focused on bringing biologics medical innovation to international markets, announced the approval of its long-acting erythropoietin, Efepoetin alfa (GX-E4), by the Indonesian Ministry of Food and Drug Safety (BPOM) for the treatment of chronic kidney disease induced anemia in non-dialysis patients. This milestone marks the first market approval for a drug originating from Genexine's research and development with KGbio. Genexine, in collaboration with KGbio, has been co-developing Efepoetin alfa for CKD patients in both non-dialysis and dialysis settings. While this BPOM approval specifically pertains to the treatment of CKD-induced anemia in non-dialysis patients, it is anticipated that further approvals for dialysis patients with CKD-induced anemia will be secured in due course. Furthermore, a multinational Phase 3 clinical trial targeting dialysis patients is set to commence in the Q4 of 2023, spearheaded by Genexine and KGbio. This study will be conducted across 11 countries in Europe and Asia to facilitate a label expansion including both dialysis and non-dialysis patient populations. “ We are thrilled to have our first-ever product approval ,” said Sungjune Hong, CEO of Genexine. “ This is a landmark result for everyone at Genexine and our partner KGbio and represents our first market approval of therapeutic drugs that have been discovered, developed, and commercialized by a Korean BioPharma company. Our efforts to focus on commercialization over the past year have been successful and we now look to roll out this product in several other Asian countries and expand the indication to include dialysis patients. Efepoetin alfa was one of the products developed using our proprietary hyFc® fusion platform and demonstrates our ability to deliver a novel long-acting EPO drug to patients suffering from CKD-induced anemia .” And President Director of PT Kalbe Genexine Biologics, Sie Djohan said “Kalbe believes by receiving market approval for anemia treatment Efepoetin alfa, It is easier for patients to get access to medicines for their recovery." In 2020, Genexine and KGbio initiated phase 3 clinical trials for non-dialysis patients in a multinational setting, spanning seven countries across Asia and Oceania. These countries included Korea, Australia, Taiwan, as well as Southeast Asian nations such as Indonesia, Malaysia, Thailand, and the Philippines. As of the latest results in April 2023, Efepoetin alfa has demonstrated non-inferiority when compared to Roche's Mircera®, exhibiting a good safety and tolerability profile. It successfully met the primary endpoint, achieving a response rate 69.6% in patients whose hemoglobin levels increased by more than 1g/dL, surpassing the 63.2% for Mircera®. About Efepoetin alfa (GX-E4) Efepoetin alfa (GX-E4) is a bio-better drug for CKD-induced anemia, developed based on hyFc ® , Genexine's proprietary long-acting platform technology. As kidney function declines patients with CKD suffer anemia due to a lack of EPO(Erythropoietin), a hormone that stimulates red blood cell production, approximately 90% of EPO is produced by the kidney. GX-E4 is a long-acting drug that extends the half-life of EPO in the body, that is developed for once every two weeks or once every four weeks injection, compared to the first-generation short-acting EPO product that needs to be injected once every 2 to 3 days. About Genexine Genexine, Inc. is a publicly traded, clinical-stage biotechnology company focused on developing and commercializing immunotherapeutic and next-generation long-acting biologics. Its primary technology platforms are Therapeutic DNA vaccine technology and hyFc® fusion technology. The Company has multiple products in clinical development including several undergoing Phase 3 registration trials. The Company's proprietary pipeline includes GX-188 (tirvalimogene teraplasmid) for cervical cancer, GX-I7 (efineptakin alfa) for multiple cancers, GX-H9 (eftansomatropin alfa) for Pediatric Growth Hormone Deficiency and GX-E4 for CKD-induced anemia, among others. Genexine has established multiple partnerships with global companies in order to expedite product development and commercialization and create significant value. Genexine is listed on the Korean exchange (KOSDAQ: 095700) and is headquartered in Seoul, Korea. Genexine is committed to the well-being and care of patients worldwide. About KGbio KGbio is a clinical-stage biotechnology company established in 2016, focused on bringing biologics medical innovation to markets outside the US/Canada, Western Europe, and China. The business model revolves around in-licensing novel biologics and select biosimilars in oncology and high-specialty therapeutic areas (typically pre-IND or early clinical stage), with the objective to out-license them in target geographies after finishing clinical development as well as regulatory and reimbursement approvals. Platforms of interest include Fc-fusion proteins, antibodies, bi-specifics, ADCs, cell therapies and therapeutic vaccines. The company is backed by Asian pharma companies Kalbe, Genexine and US private equity giant General Atlantic. For more information, kindly visit: https://www.kg-biologics.com/ About Kalbe PT Kalbe Farma Tbk. (“Kalbe”) was established in 1966 and is one of the largest publicly-listed pharmaceutical companies in Southeast Asia. Kalbe has four main divisions managing a broad and strong portfolio of brands; Prescription Pharmaceuticals Division, Consumer Health Division comprising over-the-counter drugs, as well as supplement drink and ready to drink products, Nutritional Division, and Distribution & Logistics Division. Kalbe currently has more than 40 subsidiaries and 14 production facilities with international standards, employed around 16,000 employees and have 72 branches of distribution & logistics across Indonesia. Since 1991, Kalbe’s shares have been listed on the Indonesia Stock Exchange (IDX: KLBF). As of 31 December 2022, Kalbe has IDR 28.9 trillion total consolidated revenue and IDR 98.0 trillion market capitalization. SOURCE: Genexine

CAMBRIDGE, Mass., April 28, 2021 /PRNewswire/ -- Akebia Therapeutics, Inc. (Nasdaq: AKBA), a biopharmaceutical company with the purpose to better the lives of people impacted by kidney disease, today announced that the New England Journal of Medicine (NEJM) has published the results of the global Phase 3 clinical program of vadadustat for the treatment of anemia due to chronic kidney disease (CKD) in adult patients on dialysis (INNO2VATE) and adult patients not on dialysis (PRO2TECT) in two separate manuscripts. Vadadustat, an investigational oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), is Akebia's lead product candidate. In late March 2021, the Company submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for vadadustat for the treatment of anemia due to CKD in both adult patients on dialysis and adult patients not on dialysis. "Having recently submitted our NDA for vadadustat, we are proud to have the results of our global Phase 3 clinical program published in the prestigious New England Journal of Medicine for review by the broader medical community," said Steven K. Burke, M.D., Chief Medical Officer of Akebia Therapeutics. "The publications, authored by members of the independent Executive Steering Committee in collaboration with trial investigators and Akebia, are a testament to the work of these team members who designed this program after extensive dialogue with the FDA and European regulators. We extend our deepest appreciation to everyone involved in this program, including the physicians, investigators, site coordinators, and, most importantly, the nearly 7,500 patients who participated." "The kidney community has been eagerly awaiting peer-reviewed publication of comprehensive and straight-forward analyses of cardiovascular safety and hematological efficacy results of a Phase 3 program evaluating the treatment of anemia associated with CKD with a novel HIF-PHI," said Glenn Chertow, M.D., M.P.H., Professor of Medicine at Stanford University School of Medicine, lead author of one of the manuscripts and Co-Chair of the independent Executive Steering Committee for the vadadustat global Phase 3 program. "We are honored to have vadadustat's global Phase 3 clinical program published in the New England Journal of Medicine. These publications reflect the clinical relevance, scientific rigor and transparency of the vadadustat development program." Kai-Uwe Eckardt, M.D., Professor of Medicine and Head of the Department of Nephrology and Medical Intensive Care at the Charité in Berlin, Germany, and Co-Chair of the independent Executive Steering Committee for the vadadustat global Phase 3 program, is the lead author of the INNO2VATE manuscript titled, "Safety and Efficacy of Vadadustat for Anemia in Patients Undergoing Dialysis." The manuscript states, "Among patients with anemia and CKD who were undergoing dialysis, vadadustat was noninferior to darbepoetin alfa with respect to cardiovascular safety and maintenance of hemoglobin concentrations." Dr. Chertow is the lead author of the PRO2TECT manuscript titled, "Vadadustat in Patients with Anemia and Non-Dialysis-Dependent CKD," which states, "Vadadustat, as compared with darbepoetin alfa, met the prespecified noninferiority criterion for hematologic efficacy but not the prespecified noninferiority criterion for cardiovascular safety. The New England Journal of Medicine is recognized as the world's leading medical journal and website. Published continuously for over 200 years, NEJM delivers high-quality, peer-reviewed research and interactive clinical content to physicians, educators, researchers, and the global medical community. About Akebia Therapeutics Akebia Therapeutics, Inc. is a fully integrated biopharmaceutical company with the purpose to better the lives of people impacted by kidney disease. The Company was founded in 2007 and is headquartered in Cambridge, Massachusetts. For more information, please visit our website at , which does not form a part of this release. About Vadadustat Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor designed to mimic the physiologic effect of altitude on oxygen availability. At higher altitudes, the body responds to lower oxygen availability with stabilization of hypoxia-inducible factor, which can lead to increased red blood cell production and improved oxygen delivery to tissues. Vadadustat recently completed its global Phase 3 clinical development program for the treatment of anemia due to CKD. Vadadustat is not approved by the U.S. Food and Drug Administration (FDA) or any regulatory authority with the exception of Japan's Ministry of Health, Labour and Welfare (MHLW). In Japan, vadadustat is approved and marketed under the tradename Vafseo™, as a treatment for anemia due to CKD in both dialysis-dependent and non-dialysis dependent adult patients. About Anemia due to Chronic Kidney Disease (CKD) Anemia is a condition in which a person lacks enough healthy red blood cells to carry adequate oxygen to the body's tissues. It commonly occurs in people with CKD because their kidneys do not produce enough erythropoietin (EPO), a hormone that helps regulate production of red blood cells. Anemia due to CKD can have a profound impact on a person's quality of life as it can cause fatigue, dizziness, shortness of breath and cognitive dysfunction. Left untreated, anemia leads to deterioration in health and is associated with increased morbidity and mortality in people with CKD. Investor Contact Kristen K. Sheppard, Esq. Ir@akebia.com Company Codes: NASDAQ-NMS:AKBA