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

Incidence of Alzheimer’s disease is projected to double in the next 40 years unless a cure or preventive measures are found. The U.S. Centers for Disease Control and Prevention published a new report in the journal Alzheimer’s & Dementia projecting the disease’s likely expansion, and for the first time, forecasted the disease by race and ethnicity. Incidence of Alzheimer’s disease is projected to double in the next 40 years unless a cure or preventive measures are found. The U.S. Centers for Disease Control and Prevention (CDC) published a new report in the journal Alzheimer’s & Dementia projecting the disease’s likely expansion, and for the first time, forecasted the disease by race and ethnicity. Part of the increase is simply an aging population. Alzheimer’s is presently the fifth leading cause of death in Americans age 65 and older. Currently, the burden of the disease and related dementias is cited as 1.6 percent of the U.S. population (as of 2014). It is projected, according to the CDC, to double to 3.3 percent by 2060. What that means in terms of numbers is an increase from about 5 million people with the disease to 13.9 million. Robert Redfield, director of the CDC, said in a statement, “that as the U.S. population increases, the number of people affected by Alzheimer’s disease and related dementias will rise, especially among minority populations.” The study projects that Hispanic Americans will see the biggest increase because of population growth. However, non-Hispanic whites have the most incidences of Alzheimer’s based on population figures. In Americans age 65 and older, African Americans have the highest prevalence of Alzheimer’s and dementia, ranked at 13.8 percent, followed by Hispanics at 12.2 percent, non-Hispanic whites at 10.3 percent. American Indian and Alaska Natives figure at 9.1 percent with Asian and Pacific Islanders at 8.4 percent. The study projects that by 2060, 3.2 million Hispanics and 2.2 million African Americans will have Alzheimer’s or dementia, partly due to longer life spans. The report utilized population projections from the U.S. Census Bureau , and data about the percentage of Medicare fee-for-service beneficiaries 65 and older. Redfield stated, “Early diagnosis is key to helping people and their families cope with loss of memory, navigate the health care system, and plan for their care in the future.” Despite widespread efforts by biopharma to develop drugs to treat or prevent Alzheimer’s, successful therapies remain elusive. In 2016, Jeffrey Cummings of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas and colleagues wrote in Alzheimer’s Research & Therapy, “Under the current conditions, only drugs currently in late Phase I or later could be ready by 2025, and only if the studies progress optimally. If pipeline attrition rates remain high, it is likely that only a few compounds could possibly reach this milestone. There is a great need to reduce the time and risk of AD drug development to reach the 2025 goal.” The 2025 goal was set by The Global CEO Initiative on Alzheimer’s Disease in December 2015 to find treatments and diagnostic tests for Alzheimer’s disease. It was wildly optimistic then, and three years later, it’s notable that pipeline attrition rates have, in fact, remained high, with drug after drug failing in late-stage clinical trials. Eli Lilly had a major failure of solanezumab in November 2016, and in September of the same year Lundbeck ’s idalopirdine failed in Phase III. In February 2017, Merck abandoned a Phase II/III trial of verubecestat. In September 2017, Axovant Sciences ’ intepirdine failed spectacularly. Many people are hopeful about Biogen and Eisai’ s aducanumab, which is still chugging along in various clinical trials. In late August 2018, the two companies announced results from an analysis of an ongoing long-term extension Phase Ib trial of the drug. There appears to be positive data on the drug’s effect on amyloid beta plaque levels as well as some slowing in the rate of clinical decline. The two companies also have another drug, BAN2401, that is being evaluated in Alzheimer’s. In July, Eisai disclosed seemingly positive data, although there’s a lot of disagreement among analysts as to just how positive it is, which is also the case with aducanumab. Failure after failure has left investors and analysts highly skeptical of anything but end-stage clinical data, which to date has almost always been disastrous. And meanwhile, as the CDC report notes, the population grows older and larger and the rates of Alzheimer’s and dementia are expected to grow.