Ceperognastat

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.

By Maggie Fick London: Swiss biotech company Asceneuron said on Tuesday it had raised $100 million from investors including the controlling shareholder of Wegovy maker Novo Nordisk to fund clinical development of its Alzheimer's disease drug . The Series C round was led by Novo Holdings, the investment arm of the Novo Nordisk Foundation, which will hold a board seat on the Lausanne-based company. Asceneuron's lead experimental drug ASN51 is from a new class of drugs called O-GlcNAcase (OGA) inhibitors. The company and Novo Holdings say they expect future trials to uphold their assertion that ASN51 is superior to those from the same class in development by rivals Biogen, Merck & Co and Eli Lilly. OGA inhibitors prevent the aggregation of tau proteins in the brain to slow Alzheimer's progression . They are pills and could be a companion to another class of treatments that are injections targeting the beta amyloid protein. Asceneuron will use the funds for a phase 2 trial that will begin later this year, CEO Barbara Angehrn Pavik said. Naveed Siddiqi, senior partner at Novo Holdings, said that for decades drugmakers had failed to develop effective treatments for Alzheimer's despite the large number of people suffering from it, deterring investors. But the field has recently reached an inflection point, he said, with breakthrough treatments that remove toxic proteins from the brain spurring new interest. His view echoed those of scientists and company executives interviewed by Reuters in November. A week ago Novo Holdings led a separate 90 million pound ($116.78 million) funding round for British biotech Myricx Pharma to progress its experimental cancer drugs. The wealth and influence of the Novo Nordisk Foundation is growing rapidly on the back of soaring profits from Novo Nordisk's weight-loss drug Wegovy and type 2 diabetes drug Ozempic. Novo Holdings' capital to invest is also burgeoning. Its CEO Kasim Kutay told Reuters last year that its deal size in healthcare will rise, particularly for its principal investments, which is a separate part of the firm from the venture investments group leading this month's deals. ($1 = 0.7707 pounds) (Reporting by Maggie Fick; Editing by Jan Harvey)