PDE9A

Plus, news about Idorsia, Enveda, Zymeworks, BerGenBio and Ignota Labs: Harbour BioMed does another deal: The Shanghai-based biotech’s subsidiary, called HBM Alpha Therapeutics, inked a pact with an undisclosed company for up to $395 million in upfront fees and biobucks, plus the potential for a minority stake. The undisclosed partner also gets exclusive ex-China global rights to an antibody known as HAT001/HBM9013 for congenital adrenal hyperplasia (CAH) and other rare endocrine disorders. HBMAT raised a seed round of undisclosed size in January 2023, and Harbour did a NewCo deal for an anti-TSLP antibody with Windward Bio last month. — Kyle LaHucik ORIC ‘refines’ development plans for two drugs: The ORIC-944 program is set to start a Phase 3 trial in the first half of 2026 looking at patients with metastatic castration-resistant prostate cancer. Its ORIC-114 candidate is expected to begin registrational trials sometime in 2026 in the first-line lung cancer setting. Its stock $ORIC was up about 13% on Wednesday morning. — Max Gelman Idorsia’s big updates: The Swiss drugmaker said an undisclosed party opted not to move forward with a deal for the global rights to Idorsia’s experimental hypertension drug, called aprocitentan, but it will keep the $35 million exclusivity fee that it got in December. Meanwhile, Idorsia and Viatris adjusted the terms of their collaboration for selatogrel and cenerimod, with Idorsia contributing $100 million less toward development while losing $250 million in potential milestone payments from Viatris. It is also restructuring its debt and getting new funding . — Kyle LaHucik Sanofi backs Enveda with $20M: The French pharma giant is joining the Series C of the Colorado biotech, which mines plant chemistry to find new drugs. The Series C now totals $150 million, up from the $130 million disclosed in November . — Kyle LaHucik Zymeworks’ $14M milestone: The company received the payment from GSK from a bispecific antibody deal they inked in 2016 and then expanded in 2019. — Jaimy Lee BerGenBio discontinues lung cancer study, to seek strategic alternatives: The company was evaluating whether bemcentinib, an AXL kinase inhibitor, could treat patients with first-line non-squamous non-small cell lung cancer in combination with standard of care. Patients also needed to have a mutation of the STK11 gene. In a statement, CEO Olav Hellebø said the results were not strong enough for BerGenBio to obtain additional financing and is now looking for a merger, sale or other transaction. — Max Gelman Ignota Labs closes £5.5M seed round: The startup’s goal is to “turn around failed drugs” using AI, acquiring assets from bigger companies that stopped being developed and then testing them in new clinical trials. Its first asset is a PDE9A inhibitor, which the company says has potential in cardiovascular, metabolic and neurodegenerative diseases. — Max Gelman

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Cardurion Pharmaceuticals, a biotechnology company focused on the development of novel, next-generation therapeutics for the treatment of cardiovascular diseases, today announced it has entered an exclusive licensing agreement with Astellas to develop and commercialize CRD-733, a PDE-9 inhibitor with the potential to improve cardiac function in heart failure patients. Under the terms of the agreement, Astellas has granted Cardurion Pharmaceuticals an exclusive, worldwide, royalty-bearing license to research, develop, manufacture and commercialize CRD-733 for the diagnosis, prevention and treatment of cardiovascular-related indications in humans. Heart failure is a chronic, progressive syndrome in which the heart is unable to adequately meet the body’s needs for blood and oxygen, resulting in shortness of breath, fatigue, and fluid retention. Heart failure can occur with either a weak heart muscle that cannot adequately eject blood, or a muscle that is strong enough, but other factors limiting its ability to fill or increase function, as needed, are impaired. Over 6 million people in the United States have one of these two forms of heart failure1, and this unmet medical need poses the greatest challenge in cardiovascular medicine today. Recent evidence supports that inhibition of PDE-9 has potential to restore heart-protective mechanisms that are dysfunctional in both forms of heart failure. “Heart failure is an expanding global problem that remains one of the major unmet medical needs in cardiovascular disease,” said David Kass, M.D., scientific advisor at Cardurion Pharmaceuticals and professor of medicine at the Johns Hopkins University School of Medicine, who first discovered the key role of PDE-9 inhibition in heart failure. “PDE-9 is abnormally elevated in human failing hearts, which can impede a natural protective pathway and make the heart more vulnerable to damage. In our studies, inhibiting PDE-9 was able to prevent and reverse heart malfunction brought on by abnormal stress. Inhibiting PDE-9 in patients has the real potential to treat multiple forms of heart failure2.” “Cardiovascular disease is the leading cause of death worldwide in both men and women, accounting for over 17 million deaths per year3,” said Daniel Bloomfield, chief executive officer of Cardurion Pharmaceuticals. “We are pleased to enter this agreement with Astellas to develop and commercialize CRD-733 and provide a new therapeutic option to heart failure patients. We look forward to advancing CRD-733 into further clinical development in 2018.” About Cardurion Pharmaceuticals Cardurion is a biotechnology company with both clinical and preclinical programs focused on the development of novel, next-generation therapeutics for the treatment of heart failure and other cardiovascular diseases. Led by two physician-scientists with extensive experience in cardiovascular science, medicine and drug development, Cardurion’s unique programs and strongly collaborative environment enable the company to deliver promising treatments that target major unmet needs. Cardurion has facilities in Cambridge, Massachusetts and Shonan, Japan. For more information, please visit the company’s website at . About Astellas Astellas Pharma Inc., based in Tokyo, Japan, is a company dedicated to improving the health of people around the world through the provision of innovative and reliable pharmaceutical products. Astellas focuses on Urology, Oncology, Immunology, Nephrology and Neuroscience as prioritized therapeutic areas while advancing new therapeutic areas and discovery research leveraging new technologies/modalities. Astellas is also creating new value by combining internal capabilities and external expertise in the medical/healthcare business. Astellas is on the forefront of healthcare change to turn innovative science into value for patients. For more information, please visit our website at . Cardurion’s Forward Looking Statements This press release contains forward-looking statements, all of which are qualified in their entirety by this cautionary statement. Any statements contained herein that do not describe historical facts, including, but not limited to, statements that express or imply future outcomes of our partnership with Takeda, are forward-looking statements that are based on management’s expectations and are subject to certain factors, risks and uncertainties that may cause actual results, outcomes, timing and performance to differ materially from those expressed or implied by such statements. These factors, risks and uncertainties include, but are not limited to: the costs and uncertainties associated with our research efforts and other discovery activities; the inherent uncertainties associated with the conduct, timing and results of preclinical and clinical studies of our product candidates; and the adequacy of our capital resources and availability of additional funding. Except as otherwise noted, these forward-looking statements speak only as of the date of this press release, and we undertake no obligation to update or revise any of such statements to reflect events or circumstances occurring after this press release. We caution readers not to place undue reliance on the forward-looking statements contained in this press release. The safety and efficacy of the agent discussed herein are under investigation and have not been established. There is no guarantee that the agent will receive regulatory approval and become commercially available for the uses being investigated. Information about pharmaceutical products (including products currently in development) which is included in this press release is not intended to constitute an advertisement or medical advice. 1 American Heart Association, Causes and Risks for Heart Failure (February 2018) 2 Lee, D. et al. Phosphodiesterase 9A controls nitric-oxideindependent cGMP and hypertrophic heart disease. Nature. 519, 472-476 (2015) 3 World Health Organization, Cardiovascular diseases (May 2017)

Another potential treatment for Alzheimer’s disease has been tossed into the rubbish bin. Another potential treatment for Alzheimer’s disease has been tossed into the rubbish bin. This morning, Boehringer Ingelheim announced it was scrapping its Phase II investigational compound BI 409306 after it failed to meet endpoints. Germany-based Boehringer Ingelheim said it was studying the effects of BI 409306, a PDE9 inhibitor, in patients with cognitive impairment and those with memory dysfunction in schizophrenia and in Alzheimer’s disease. In its efforts to treat Alzheimer’s, Boehringer Ingelheim was attempting to determine the efficacy BI 409306 had on targeting glutamate, a neurotransmitter. In two studies, Boehringer Ingelheim said BI 409306 failed to demonstrate superiority over placebo in cognition. The trials included 457 patients who received either the Boehringer Ingelheim compound or placebo for a period of 12 weeks. BI 409306 is designed to block the PDE9A protein. By doing so, researchers hoped to enhance the glutamatergic signaling pathways in the brain to increase synaptic strength and plasticity. The glutamatergic pathways are thought to affect brain functions that are important to memory and learning. Boehringer did not disclose what it actually discovered in the Phase II trial or why the compound missed its mark. The company said it intends to share topline data results at the Alzheimer’s Association International Conference in July. Further analysis will be needed to fully understand the results and how best to shape future research in Alzheimer’s disease, the company said. Jan Poth , the therapeutic head of CNS diseases at Boehringer Ingelheim, said there is great anticipation in any research that could provide solutions to forms of dementia, such as Alzheimer’s. While there is hope in research, Poth took it in stride that failure is also part of the game as well. “However, this is what research is about: disappointments are a daily experience in science, but even these clinical trial results will add to the understanding of brain function and contribute to future progress in this area,” Poth said in a statement. Although Boehringer Ingelheim said it no longer intended to focus resources on determining if BI 409306 could have an effect on Alzheimer’s, the company said it could still be an effective treatment for schizophrenia. Future investigations of BI 409306 will focus on two studies in schizophrenia, aimed at prevention of relapse and at prevention of occurrence of a first psychotic episode. Boehringer Ingelheim said the failure of BI 409306 will not deter its efforts to develop a treatment for dementia patients. The company is planning a Phase II trial with another compound, BI 425809, a GlyT1 inhibitor, in a range of central nervous system (CNS) indications which also include Alzheimer’s disease. Dementia is one of the most serious CNS issues. In 2017, the number of people believed to be living with some form of dementia is 50 million. This number will double almost every 20 years, reaching 75 million by 2030 and 131.5 million by 2050. Boehringer is part of the “We won’t rest” initiative in Europe that is aimed at developing lasting therapies for dementia, schizophrenia and other disorders. “Starting from our systematic neurobiological approach to CNS research, we will continue to build innovative approaches in our clinical trials and help advance the field in collaboration with the wider scientific community. We won’t rest,” Stephane Pollentier , Boehringer’s head of CNS, said in a statement.