Vocimagene amiretrorepvec

SAN DIEGO, April 30, 2024 /PRNewswire/ -- Denovo Biopharma LLC (Denovo), a pioneer in applying precision medicine to the development of innovative therapies, today announced that the California Institute for Regenerative Medicine (CIRM) has awarded a $11.8M grant for further development of DB107, Denovo's DGM7™ biomarker–guided late–stage gene therapy, for high–grade glioma (HGG) including glioblastoma (GBM), a malignant brain cancer. CIRM has awarded the grant to Dr. Noriyuki Kasahara, MD, PhD, at the University of California San Francisco (UCSF) and a group of investigators at California universities to conduct a Phase 1/2 clinical trial studying DB107 in patients with newly–diagnosed HGG. Continue Reading The trial, titled "A Phase I/IIa Study to Evaluate the Efficacy of DB107–RRV, Administered to Subjects at Time of Resection and Intravenously Thereafter, in Combination with DB107–FC and Radiation Therapy or DB107–FC, Temozolomide (TMZ) and Radiation Therapy in Patients with Newly–Diagnosed High–Grade Glioma," plans to enroll up to 70 patients. The trial aims to demonstrate improvements in progression–free survival. We are thrilled to continue the clinical development of our biomarker-guided DB107 gene therapy in HGG including GBM. Post this DB107 consists of two components: DB107–RRV (vocimagene amiretrorepvec) as a prodrug activator gene therapy and DB107–FC (extended-release 5–fluorocytosine [5–FC]) as an oral prodrug. DB107–RRV, a retroviral replicating vector (RRV) administered intratumorally and intravenously, converts the orally administered 5–FC into the potent chemotherapy agent 5–fluorouracil (5–FU) locally at the tumor sites. This enables intratumoral concentrations 30–50 times of those achievable by 5–FU systemic administration, killing tumor cells while minimizing the systemic exposure and off–target toxicities of 5–FU. Using its proprietary biomarker discovery platform including whole genome sequencing (WGS) and artificial intelligence (AI), Denovo discovered the novel germline genetic biomarker, Denovo Genomic Marker 7 (DGM7), which is located in the SHROOM3 gene intron. Retrospective analysis of an earlier randomized clinical trial in patients with recurrent HGG suggested improved overall survival in DGM7–positive patients treated with DB107. "We are excited to conduct this novel trial which will be investigating several new approaches for the first time in patients with newly–diagnosed high–grade glioma. In addition to DB107–RRV being administered both intratumorally and intravenously to provide more exposure, this study will also use the RRV in conjunction with radiation therapy and chemotherapy with temozolomide. In addition to the direct therapeutic effect of gene therapy, glioma cells will be sensitized to these standard therapies by 5–FU generated directly within the patient's tumor from DB107–FC. We are also excited to test the DGM7 biomarker to see if we can identify patients who may benefit the most from this unique gene therapy approach," said Dr. Kasahara. DGM7 status will be determined at the time of enrollment to prospectively assess the effect of the biomarker on clinical outcomes. The study will be conducted at UCSF (Dr. Noriyuki Kasahara, MD, PhD, and Dr. Nicholas Butowski, MD), University of Southern California (USC) (Dr. Thomas Chen, MD, PhD), and University of California San Diego (UCSD) (Dr. David Piccioni, MD, PhD), and will be managed by Anova Enterprises, Inc. "We are thrilled to continue the clinical development of our biomarker–guided DB107 gene therapy in patients with HGG including GBM, a major unmet medical need with less than 5% of GBM patients surviving 5 years," said Dr. Matthew A. Spear, MD, Denovo's Chief Medical Officer and Chief Development Officer. "Alongside our recent announcement of positive results in a Phase 2b clinical trial of our DGM4 biomarker–guided DB104 drug (liafensine) in treatment–resistant depression, the CIRM grant provides continued validation of Denovo's approach to discovering new genetic biomarkers and developing biomarker–guided therapies." About HGG and GBM The most common type of high–grade glioma (HGG) is glioblastoma (GBM), which is also the most common type of adult primary brain cancer, with 18,000 newly–diagnosed patients in the US and 13,000 deaths annually. Standard treatments for patients with newly–diagnosed GBM can include surgery followed by radiation and chemotherapy, but treatment options are limited. The 5–year survival rate of patients with GBM is less than 5%. About DB107 and the DGM7™ Biomarker DB107 is an investigational combination product consisting of the DB107–RRV (vocimagene amiretrorepvec) gene therapy and DB107–FC (extended–release 5–fluorocytosine) oral prodrug. DB107–RRV, an innovative proprietary retroviral replicating vector (RRV), is combined with DB107–FC to selectively infect and kill cancer cells while stimulating a robust and durable anti–cancer immune response against a tumor with minimal toxicity. DB107 has been tested clinically in solid tumors including recurrent high–grade glioma (rHGG) and colorectal cancer, most recently in a randomized 403–patient Phase 2/3 trial in rHGG including glioblastoma (GBM). Using its proprietary biomarker discovery platform, Denovo discovered the novel genetic biomarker, DGM7, which has been shown to be associated with treatment response to DB107 in patients with rHGG including GBM. DB107 has received Fast Track Designation and Breakthrough Therapy Designation from the FDA, as well as Orphan Drug Designations from the FDA and EMA. About Denovo Biopharma Denovo Biopharma LLC (Denovo) is a clinical–stage biopharmaceutical company that uses a novel biomarker discovery platform including whole genome sequencing (WGS) and artificial intelligence (AI) to find new genetic biomarkers predictive of drug efficacy, and then uses these biomarkers to execute efficient clinical trials in targeted patient populations to increase the probability of success. Denovo has eight late–stage drugs in its pipeline addressing major unmet medical needs in oncology and central nervous system diseases; most of the pipeline are first–in–class drugs with global rights. Denovo recently announced a major breakthrough in treatment–resistant depression (TRD) with its DGM4™ biomarker–guided DB104 drug (liafensine, a potential first–in–class triple reuptake inhibitor for TRD). The global Phase 2b clinical trial of DB104 in DGM4–positive patients with TRD demonstrated strikingly positive results, with highly significant improvements in symptoms of depression seen in DGM4–positive patients. Visit for additional information. Contact Michael F. Haller, Chief Business Officer Denovo Biopharma LLC [email protected] SOURCE Denovo Biopharma LLC

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