Entera Bio Ltd.

March 17, 2025 -- OPKO Health, Inc. (NASDAQ: OPK) and Entera Bio Ltd. (NASDAQ: ENTX), a leader in the development of oral peptides and proteins replacement therapies, entered into a collaboration and license agreement to advance into the clinic the first oral dual agonist GLP-1/glucagon peptide as a once-daily tablet treatment for patients with obesity, metabolic and fibrotic disorders. The program combines OPKO’s proprietary long-acting oxyntomodulin analog (OPK-88006) and Entera’s proprietary N-Tab™ technology. Favorable pharmacodynamic, pharmacokinetic and bioavailability data in vivo were reported in September 2024. The companies expect to file an Investigational New Drug application with the U.S. Food and Drug Administration (FDA) later this year. Under the terms of the agreement, OPKO and Entera will hold 60% and 40% pro-rata ownership interests, respectively, in the program and be responsible for 60% and 40% of the program’s development costs, respectively. In connection with the execution of the agreement, OPKO purchased 3,685,226 ordinary shares of Entera for a purchase price equal to $2.17 per share. Entera has agreed to utilize the proceeds from the sale of the shares to fund its 40% share of costs through Phase 1 of the development program. Following the completion of the Phase 1 stage, Entera has the option to continue to fund its 40% share to maintain its pro-rata ownership interest of the program. Should Entera opt-out, Entera will retain a 15% ownership interest in the Oral OXM program, while OPKO will retain 85% and be responsible for ongoing development activities and funding of the program. “We are pleased to continue working with Entera on this promising program to develop the first oral GLP-1/glucagon dual agonist in addition to our subcutaneous injectable dual agonist GLP-1/glucagon program. Our goal with this franchise is to provide additional options for patients with obesity, metabolic and fibrotic diseases,” said Phillip Frost, M.D., Chairman and Chief Executive Officer of OPKO. “We have enjoyed our synergistic partnership with OPKO. This expanded collaboration on the GLP-1/glucagon program reinforces our shared vision to develop first in class differentiated oral peptide treatments for patients to better manage their health,” said Miranda Toledano, Entera Chief Executive Officer. Oxyntomodulin is a naturally occurring GLP-1/glucagon dual agonist peptide hormone found in the small intestine that acts to suppress appetite, induce weight loss and has additional cardioprotective and anti-fibrotic attributes. OPK-88006 is a GLP-1/glucagon dual agonist peptide that has been modified to maintain its long-acting profile while increasing its potential potency. Currently, there are no approved dual GLP-1/glucagon agonists available. Entera is a clinical stage company focused on developing oral peptide and protein replacement therapies for significant unmet medical needs where an oral tablet form holds the potential to transform the standard of care. The Company leverages on a disruptive and proprietary technology platform (N-Tab™) and its pipeline includes five differentiated, first-in-class oral peptide programs targeting PTH(1-34), GLP-1 and GLP-2. The Company’s most advanced product candidate, EB613 (oral PTH(1-34)), is being developed as the first oral, osteoanabolic (bone building) once-daily tablet treatment for post-menopausal women with low BMD and high-risk osteoporosis. A placebo controlled, dose-ranging Phase 2 study of EB613 tablets (n=161) met primary (PD/bone turnover biomarker) and secondary endpoints (BMD). Entera is preparing to initiate a Phase 3 registrational study for EB613 pursuant to the FDA’s qualification of a quantitative BMD endpoint. The EB612 program is being developed as the first oral PTH(1-34) tablet peptide replacement therapy for hypoparathyroidism. Entera is also developing the first oral oxyntomodulin, a dual targeted GLP-1/glucagon peptide, in tablet form for the treatment of obesity; and first oral GLP-2 peptide tablet as an injection-free alternative for patients suffering from rare malabsorption conditions such as short bowel syndrome in collaboration with OPKO Health. OPKO Health is a multinational biopharmaceutical and diagnostics company that seeks to establish industry-leading positions in large, rapidly growing markets by leveraging its discovery, development and commercialization expertise, and its novel and proprietary technologies. The content above comes from the network. if any infringement, please contact us to modify.

The agreement involves the development of the first oral glucagon-like peptide-1/glucagon dual agonist to offer obesity treatments. Credit: fizkes/Shutterstock. Opko Health and Entera Bio have announced a partnership and licence agreement to progress the development of the first oral dual agonist glucagon-like peptide-1 (GLP-1)/glucagon, aiming to provide treatment for individuals with metabolic, fibrotic and obesity disorders. The programme unites Opko’s long-acting oxyntomodulin (OXM) analogue, OPK-88006 and Entera’s N-Tab technology. Opko will hold 60% and Entera 40% ownership interests. The partnership will account for the corresponding percentage of the programme’s development expenses. In conjunction with the agreement, Opko has invested in Entera, purchasing 3.69 million ordinary shares at $2.17 each. Entera plans to use the proceeds to fund its share of costs via Phase I of the development programme. After the Phase I stage conclusion, Entera may choose to continue funding its share to maintain ownership interest or opt out, in which case it will retain a 15% stake in the oral OXM programme, while Opko will hold 85% and manage further development and funding. OXM is a hormone that suppresses appetite and induces weight loss, with extra cardioprotective and anti-fibrotic properties. The companies anticipate submitting an investigational new drug application to the US Food and Drug Administration in 2025. Opko Health CEO and chairman Phillip Frost stated: “We are pleased to continue working with Entera on this promising programme to develop the first oral GLP-1/glucagon dual agonist in addition to our subcutaneous injectable dual agonist GLP-1/glucagon programme.” Israel-based clinical-stage company Entera develops protein replacement therapies and oral peptides. Its technology platform, N-Tab, supports a pipeline of five oral peptide programmes. Entera Bio CEO Miranda Toledano stated: “We have enjoyed our synergistic partnership with Opko. This expanded collaboration on the GLP-1/glucagon programme reinforces our shared vision to develop first-in-class differentiated oral peptide treatments for patients to better manage their health.”

Opko Health said a planned phase 1 study would mark the first time that an orally administered GLP-1/glucagon agonist would enter human trials.\n Opko Health and Entera Bio have formalized their partnership as the biotechs prepare to take the first orally administered dual agonist glucagonlike-peptide 1 (GLP-1)/glucagon peptide into the clinic.The once-daily pill combines Opko’s long-acting GLP-1/glucagon dual agonist peptide, dubbed OPK-88006, with Entera’s N-Tab oral delivery tech. The companies’ current timetable would involve seeking permission from the FDA “later this year” to enter human trials, according to a March 17 release.The agreement will see Miami-based Opko and Israel-based Entera holding 60% and 40% ownership, respectively, in the program, and sharing the development costs by the same ratio.Opko will also buy 3.6 million shares of Entera at $2.17 a pop, slightly above the $1.88 price at which the shares closed after Friday’s trading. Entera will use the proceeds to help fund its side of the development costs through to the phase 1 trial.Beyond that first human study, Entera will then have the option to continue to fund its side of the development in order to retain its part of the program’s ownership. If the biotech decides at this point to opt out, it will still keep a 15% ownership interest, with Opko accounting for the remaining 85% while taking on the full development and funding burden.The two blockbuster obesity drugs already on the market are Novo Nordisk’s GLP-1 agonist Wegovy and Eli Lilly’s dual GLP-1/GIP agonist Zepbound. However, there are not yet any approved therapies that follow Opko’s modality of simultaneously activating the GLP-1 and glucagon receptors.Big Pharmas have tended to evaluate dual GLP-1/glucagon co-agonists as potential treatments for metabolic dysfunction-associated steatohepatitis (MASH). AstraZeneca has its own candidate, dubbed AZD9550, in phase 1 development for the liver condition, while Merck & Co.’s efinopegdutide beat Wegovy in the related condition of nonalcoholic fatty liver disease in a phase 2 trial.Opko said taking their drug into the clinic this year would mark the first time an orally administered GLP-1/glucagon agonist would enter human trials. The hope is that the med can be used as a once-daily table treatment for patients with obesity as well as metabolic and fibrotic disorders. Opko and Entera have already been collaborating on the obesity drug as well as on an oral GLP-2 peptide tablet they hope will offer an injection-free alternative for patients suffering from rare malabsorption conditions such as short bowel syndrome.“We are pleased to continue working with Entera on this promising program to develop the first oral GLP-1/glucagon dual agonist in addition to our subcutaneous injectable dual agonist GLP-1/glucagon program,” Onko’s CEO Phillip Frost, M.D., said in the release. “Our goal with this franchise is to provide additional options for patients with obesity, metabolic and fibrotic diseases.”