LY-3372689

None The confetti is still flying from Eli Lilly’s party celebrating the approval of Alzheimer’s disease therapy donanemab, but the company is yet again facing the harsh reality of the neurodegenerative disease with the failure of an early tau-targeting med.Lilly Chief Scientific Officer and President, Lilly Research Laboratories Daniel Skovronsky, M.D., Ph.D., said the O-GlcNAcase Inhibitor called LY3372689 failed on the primary endpoint of a phase 2 clinical trial recently. The therapy, which targets the OGA enzyme, did not spur a change in baseline to endpoint time in a rating scale of Alzheimer’s severity in either dose tested.“While this negative outcome was disappointing, we remain committed to tap as a high conviction target in Alzheimer's disease and plan to continue studying tau biology,” Skovronsky said, speaking on a second-quarter earnings call Thursday. The executive said the company is currently reviewing the data for presentation at an upcoming medical conference.LY3372689 was a key part of Lilly’s next wave of Alzheimer’s efforts. After getting donanemab approved in July, to be marketed as Kisunla, the company was hoping that tau would be the next front in the fight against the memory-robbing disease. Behind Kisunla, Lilly has remternetug in phase 3 development, which targets amyloid plaques in the brain. Positive allosteric modulator mevidalen is in phase 2 testing. The company also has two undisclosed neurodegeneration medicines in phase 1.Lilly also trimmed around the edges of other programs after getting some early data on a few candidates.They include LOXO-783, a highly mutant-selective, brain-penetrant, allosteric small molecule PI3Kα H1047R inhibitor that was acquired as part of the acquisition of Loxo Oncology. The drug was being investigated in a phase 1 study in patients with PIK3CA H1047R-mutant advanced breast cancer and other solid tumors.Lilly had taken LOXO-783 into the clinic on the basis of preclinical data showing activity without on-target wild-type PI3Kα mediated toxicity.“We evaluated the ongoing clinical data for the program and compared the molecule to next-generation candidates that we have progressed from our discovery efforts,” Skovronsky said on the call. “We believe our next molecules have greater potential benefits to patients.”Also on the discard pile is an unnamed NRG4 agonist. Neuregulin 4 acts locally on brown and white adipose tissue and works to protect against obesity-related inflammatory and hypoxic events. The Big Pharma had halted work on the asset as “the profile is insufficient for further clinical development,” Skovronsky explained. A GITR antagonist has also been removed from the phase 1 immunology pipeline “due to insufficient efficacy,” Skovronsky said. At the time of publication, Lilly had not confirmed to Fierce whether this was LY3461767, a GITR antagonist that was being evaluated in a phase 1 trial of the drug in patients with chronic heart failure with reduced ejection fraction.Acadamic researchers have named glucocorticoid-induced tumor necrosis factor receptor (GITR), a co-stimulatory immune checkpoint protein, as playing a pivotal in cardiovascular disease. It’s also been suggested as a potential target to enhance immunotherapy, in particular immune checkpoint inhibitors.

Consortium brings together industry, academic, and regulatory experts to advance research and bridge gaps in drug development targeting Alzheimer's disease Asceneuron to contribute its expertise in neurodegenerative disease to advance biomarkers for drug development in Alzheimer's disease LAUSANNE, Switzerland and SAN FRANCISCO, March 26, 2024 /PRNewswire/ -- Asceneuron SA, a clinical stage biotech company dedicated to targeting the root causes of neurodegenerative diseases, today announces that it has joined the Critical Path Institute's, Critical Path for Alzheimer's Disease (CPAD) Consortium. With its highly experienced leadership team and world class Scientific Advisory Board of leading experts in neurodegenerative diseases, Asceneuron is well positioned to contribute to the consortium. Asceneuron has an exemplary pipeline of O-GlcNAcase (OGA) inhibitors in clinical development that have the potential to halt disease progression in neurodegenerative diseases. Its lead asset, ASN51, is a potential best-in-class, orally administered, OGA inhibitor targeting tau aggregation and will be progressing into Phase II clinical development later this year. The CPAD consortium is proceeding to advance important biomarkers for Alzheimer's disease (AD), such as tau Positron Emission Tomography (PET) and is accelerating the pathway for approval of promising new therapies. As a member of CPAD, Asceneuron will work collaboratively with the consortium to help address the large unmet medical need of patients and families suffering due to neurodegenerative diseases. Ryan Schubert, Senior Vice President Research and Development at Asceneuron, said: "We are honored to be collaborating with the CPAD consortium alongside esteemed fellow members, all of whom are dedicated to accelerating drug development to improve patients' lives. CPAD has gathered high quality data and experts from industry, academia and regulatory agencies with a focus on bringing new treatment options to patients suffering with AD. We look forward to contributing to and impacting the treatment pathway for AD as we advance our lead intracellular tau-targeting asset, ASN51, into Phase II clinical development later this year. Further information will be shared at upcoming scientific conferences." Yashmin Karten, PhD, MBA, Associate Director at Critical Path for Alzheimer's Disease, added: "C-Path is proud to welcome Asceneuron as the newest member of its CPAD Consortium. Asceneuron's research on molecules that prevent the formation of toxic tau aggregates in the brain to slow down or stop the progression of AD provides a welcome addition to the intellectual brain power and wealth of scientific knowledge within the consortium. CPAD's diverse stakeholders and members are dedicated to enhancing regulatory decision-making tools to advance drug development and improve the lives of those living with AD and related dementia (ADRD). CPAD's mission is to accelerate the drug development process for patients with chronic neurodegenerative disease leading to dementia. Its primary focus is on AD. CPAD works with industry, regulatory authorities, academia, and patient advocacy organizations to aggregate anonymized patient-level data consensus standards with the aim of advancing drug development tools for evaluating drug efficacy and safety, to optimize novel clinical trial designs, and facilitating the regulatory review process." CPAD's integrated and standardized patient-level database comprises over 100,000 patient level records across 73 separate clinical trial datasets. These records are utilized by over 370 institutions worldwide. Alongside its biotech and pharmaceutical company members, the initiative incorporates feedback from all its stakeholders, including government and regulatory agencies. CPAD has ongoing efforts as part of its pre-competitive working groups to evaluate the potential of tau PET as a reliable surrogate endpoint, with the aim of enhancing efficiency in Alzheimer's disease drug development. About Asceneuron Asceneuron is a clinical stage biotech company focused on the development of orally bioavailable therapeutics for debilitating neurodegenerative disorders with high unmet medical need. The company's pipeline reflects its ambition and commitment to developing treatments for a wide a range of neurodegenerative diseases including Alzheimer's and Parkinson's disease, as well as orphan tauopathies. Asceneuron has two clinical-stage small molecule O-GlcNAcase inhibitors in development for the treatment of proteinopathies: OGA inhibitor ASN90 (licensed to Ferrer Pharmaceuticals) for the treatment of progressive supranuclear palsy (PSP) and a potential best-in-class OGA inhibitor, ASN51 for Alzheimer's disease. Asceneuron is backed by a renowned syndicate of investors consisting of Sofinnova Partners, M Ventures, SR One, Johnson & Johnson Innovation – JJDC, Inc. (JJDC) and Kurma Partners. For more information, please visit . About Critical Path Institute Critical Path Institute (C-Path) is an independent, nonprofit established in 2005 as a public-private partnership, in response to the FDA's Critical Path Initiative. C-Path's mission is to lead collaborations that advance better treatments for people worldwide. Globally recognized as a pioneer in accelerating drug development, C-Path has established numerous international consortia, programs and initiatives that currently include more than 1,600 scientists and representatives from government and regulatory agencies, academia, patient organizations, disease foundations and pharmaceutical and biotech companies. With dedicated team members located throughout the world, C-Path's global headquarters is located in Tucson, Arizona and C-Path's Europe subsidiary is headquartered in Amsterdam, Netherlands. For more information, visit . About Critical Path for Alzheimer's Disease (CPAD) Consortium Founded in 2008, the Critical Path for Alzheimer's Disease (CPAD) enhances regulatory decision-making tools to advance drug development and improve the lives of those living with Alzheimer's disease and related dementia (ADRD). The primary objective of Critical Path for Alzheimer's Disease (CPAD), a pre-competitive consortium of the Critical Path Institute, is to promote, support, and manage data and knowledge sharing from Alzheimer disease (AD) drug development stakeholders. CPAD generates the appropriate tools for the specific challenges identified by our stakeholders, to accelerate drug development for AD and advancing better treatments for people worldwide. For more information, please visit . SOURCE Asceneuron SA