OGA

UCB will advance its anti-tau antibody for Alzheimer’s disease solo after Roche and Genentech walked away from the asset known as bepranemab. In 2020, Roche and Genentech spent $120 million upfront and committed up to $2 billion in milestones and royalties for exclusive rights to the candidate, a monoclonal antibody that targets the buildup of tau protein in the brain. On Tuesday, UCB said it regained global rights to bepranemab after the partnership ended. This is not the first time Roche and Genentech have opted out of the anti-tau space. In January, the companies ended a two-decade-long Alzheimer’s partnership with AC Immune after several lackluster readouts, leaving behind an asset targeting amyloid and another one targeting tau. Bepranemab is currently in Phase 2a, with topline data to be presented at the Clinical Trials on Alzheimer’s Disease annual meeting in Madrid later this month. The trial is testing the effects of two doses of bepranemab administered every four weeks versus placebo in people with prodromal or mild Alzheimer’s. Earlier this month, Leerink analysts said positive results for bepranemab could “incrementally de-risk” next-generation anti-tau antibodies. The buildup of tau in the brain creates “tangles” that are thought to trigger cell damage and inflammation in Alzheimer’s. Pharma companies such as Roche and Eli Lilly took an interest in targeting tau several years ago when drugs that zero in on amyloid beta were struggling in the clinic. But the tau approach has yielded mixed results. Lilly’s tau-targeting OGA inhibitor failed a Phase 2 study in August. Biogen’s antisense oligonucleotide asset designed to reduce tau showed hints of efficacy in an early-stage trial late last year. As for Roche, the deal termination comes as part of a broader strategy shift that focuses on cardiometabolic, oncology and neurology drugs. The company has notably made investments in next-generation weight loss approaches . Genentech is still into anti-tau modalities. In August, it spent $50 million in near-term licensing fees and milestones to work with Sangamo on an epigenetic repressor to prevent the production of the protein. Editor’s Note: This article has been updated to correct that Genentech spent $50 million on its deal with Sangamo. A previous version stated it spent $350 million upfront.

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.

EQT Life Sciences has invested in Asceneuron's oversubscribed Series C and Prof. Philip Scheltens will join the Asceneuron Board of Directors Asceneuron - which is developing small molecules targeting tau protein aggregation, a root cause of neurodegenerative disease - will use the funds to progress its lead asset ASN51 into Phase 2 clinical development for the treatment of Alzheimer's disease AMSTERDAM, July 16, 2024 /PRNewswire/ -- EQT Life Sciences is pleased to share that the LSP Dementia Fund has invested in Asceneuron SA ("Asceneuron" or "the Company"), a clinical stage biotech company developing small molecules, targeting tau protein aggregation, a root cause of neurodegenerative disease. New investors in the oversubscribed USD 100 million Series C also include Novo Holdings – which led the round – OrbiMed and SR One. Existing investors M Ventures, Sofinnova Partners, GSK Equities Investments Limited and Johnson & Johnson Innovation also participated. Prof. Philip Scheltens, Partner and Head of the LSP Dementia Fund, will join the Asceneuron Board of Directors, and Dr. Arno de Wilde, Director at the Fund will join as board observer. The financing will be used to advance the clinical development of Asceneuron's clinical pipeline of OGA inhibitors for the treatment of neurodegenerative diseases. Primarily, Asceneuron plans to take its lead asset, known as ASN51, into Phase 2 clinical development for the treatment of Alzheimer's disease. ASN51 is an oral small molecule drug designed to inhibit OGA, an enzyme implicated in protein aggregation. By preventing the aggregation of tau proteins, ASN51 aims to slow the progression of Alzheimer's disease. OGA inhibition has also shown promise in the prevention of other neurodegenerative diseases, including Parkinson's disease and amyotrophic lateral sclerosis. Asceneuron has completed five early-stage clinical trials, showing that their treatment effectively reaches the brain and targets the OGA enzyme. Asceneuron plans to initiate its first Phase 2 clinical study later this year. Barbara Angehrn Pavik, Chief Executive Officer of Asceneuron, said: "This high caliber life sciences investor syndicate further validates the potential of our OGA inhibitor pipeline and leadership in the field of tauopathies. We are excited to be working with the LSP Dementia Fund given their outstanding track record in the field of Alzheimer's disease as we advance our lead asset ASN51 into Phase 2 clinical development, recognizing its potential to significantly expand treatment options for patients with Alzheimer's disease". New Asceneuron Board Member and Head of the LSP Dementia Fund Prof. Philip Scheltens added: "Dementia and other neurodegenerative diseases are some of the greatest healthcare challenges of our time. With our LSP Dementia Fund, EQT Life Sciences can invest in innovative companies across the neurodegenerative spectrum. Asceneuron is exactly this kind of company. Its clinical pipeline has breakthrough potential to change patients' lives for the better and we're delighted to be joining Asceneuron on its journey." Contact EQT Press Office, [email protected] This information was brought to you by Cision The following files are available for download: