Idalopirdine

SAN DIEGO, July 1, 2021 /PRNewswire/ -- Denovo Biopharma LLC, a pioneer in applying precision medicine to develop innovative therapies, today announced it has licensed global rights for idalopirdine from H. Lundbeck A/S, including all rights to develop, manufacture and commercialize idalopirdine for all indications. Lundbeck received options to re-acquire idalopirdine for predetermined undisclosed financial terms, with Denovo and Lundbeck sharing China rights in the event Lundbeck's options are exercised and Denovo retaining all global rights in the event Lundbeck's options are not exercised. Terms of the agreement were not disclosed. Idalopirdine (now DB109) is an oral antagonist of the serotonin (5-HT6) receptor, which is primarily expressed in the brain and is hypothesized to be involved in Alzheimer's Disease, schizophrenia, and other indications. DB109 has been extensively evaluated in numerous clinical studies encompassing more than 2500 subjects. Although Phase 3 trial results were negative, subsets of patients who showed signs of beneficial activity of DB109 were identified. Despite the recent approval of aducanumab, Alzheimer's Disease remains one of the toughest diseases to conquer as countless drug have failed to demonstrate efficacy. While precision medicine has proved to vital to the many breakthroughs in oncology drug development in the last decade, the lack of pharmacogenomic biomarkers could be one of the main reasons of these failures in Alzheimer's Disease. Denovo plans to use its unique biomarker platform to search for pharmacogenomic predictors of DB109's efficacy. "Alzheimer's Disease remains an area of significant unmet need in neurological disease, and the rich idalopirdine data set that has been generated permits Denovo to fully leverage its experience in novel biomarker discovery to potentially identify patients for which idalopirdine may have benefit," said Michael F. Haller, Ph.D., Denovo's Chief Business Officer. "Denovo discovered the first known genetic biomarker for drug efficacy in a CNS disorder, for our DB104 asset in treatment-resistant depression, and we hope to have similar success for DB109." "We are excited to collaborate with Denovo Biopharma and build upon the efforts of our employees, investigators, and patients who participated in our clinical trials to potentially develop a personalized medicine for Alzheimer's Disease," said Keld Flintholm Jørgensen, CBO at Lundbeck. About Denovo Biopharma LLC Denovo Biopharma is a clinical-stage biopharmaceutical company that applies novel biomarker approaches to re-evaluate medicines that have failed in broad patient populations. The company seeks to discover genomic biomarkers correlated with patients' responses to drug candidates retrospectively. Denovo then designs and executes efficient clinical trials in targeted patient populations to optimize the probability of a successful trial. Denovo has completed enrollment of patients in the U.S. and China with diffuse large B-cell lymphoma (DLBCL) in a Phase 3 clinical trial and has an ongoing Phase 3 trial in Glioblastoma (GBM) for its lead product candidate, DB102 (enzastaurin), which was in-licensed from Eli Lilly & Co. The company has seven additional late-stage programs targeting major unmet needs: DB103 (pomaglumetad methionil) for schizophrenia, DB104 (liafensine) for depression, DB105 (ORM-12741) for Alzheimer's Disease, DB106 (vosaroxin) for acute myeloid leukemia (AML), DB107 (Toca 511 and Toca FC) for recurrent high grade glioma, DB108 (endostatin) for non-small cell lung cancer (NSCLC), and DB109 (idalopirdine) for Alzheimer's Disease. For additional information please visit . Contact: Michael F. Haller, Chief Business Officer Denovo Biopharma LLC mhaller@denovobiopharma.com

Seven months after Lundbeck and Otsuka reported a Phase III flop for their Alzheimer’s drug idalopirdine, the partners are back with a hit-and-miss score on easing Alzheimer’s agitation for their blockbuster therapy Rexulti (brexpiprazole). Already approved for schizophrenia and major depression, the collaborators were looking for the first approval of an antipsychotic specifically for agitation triggered by Alzheimer’s dementia, a condition that afflicts millions of people in the US and millions more worldwide. Agitation can be expressed in many ways, running from wandering to aggressive behavior. But in trying to gain positive data regulators want to see from two big late-stage studies, researchers scored a hit on the primary — change from baseline in the Cohen-Mansfield Agitation Inventory total score — in one study but missed in the second, though the drug did achieve the key secondary endpoint assessing the severity of agitation. Is it enough for an approval? Lundbeck didn’t spell out the data, which makes this too tough to call. Regulators have been signaling their flexibility when it comes to Alzheimer’s, a field which has seen nothing but failure for disease modifying and symptomatic drugs over the last 15 years. So it’s a possibility. With Rexulti on the market already, and likely in use for dementia-related agitation, analysts were expecting a clear win. But it may just come down to the safety profile. “Importantly, in the two Rexulti studies overall mortality was low (0.86%) with no deaths considered to be treatment related,” noted Jefferies’ Peter Welford. He added: Lundbeck and partner Otsuka plan to meet with the FDA to discuss these Rexulti data. Typically we believe regulatory authorities require two positive studies to support approval but we note equivocal study outcomes are common in CNS indications. Furthermore, no drugs are US approved specifically to treat agitation associated with dementia, despite the widespread use of antipsychotics. Rexulti’s comparatively clean safety profile could potentially allay class-wide concerns and numerous initiatives are ongoing to decrease the off-label use of antipsychotics in nursing homes. One likely line that the companies will take focuses on their takeaway that the data varied by country. The data separation between placebo and drug was particularly poor in Russia, they said, which could be due to standard of care rather than the quality of the medicine. Russia and Eastern Europe have been regularly held out as problematic locations for drug trials, which makes you wonder why Lundbeck and Otsuka’s team decided to include the country in a worldwide trial in the first place. It will be up to the FDA now to signal which way this application could go. The two partners have been vexed by Alzheimer’s, like most other companies in this field. They recently wrote off their 5HT6 symptomatic drug after it flopped in studies. Antipsychotics, though, are not your run-of-the-mill kind of Alzheimer’s drug, opening up some new opportunities to follow.