Liafensine

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

ENLIGHTEN, a genetic biomarker–guided global late–stage clinical trial of DB104 (liafensine) for treatment–resistant depression, successfully met all major study endpoints SAN DIEGO, April 3, 2024 /PRNewswire/ -- Denovo Biopharma LLC (Denovo), a pioneer in applying precision medicine to the development of innovative drugs, today announced positive results for its biomarker–guided Phase 2b clinical trial (ENLIGHTEN) designed to assess the efficacy and safety of DB104 (liafensine) in patients with treatment-resistant depression (TRD). Continue Reading More than 23 million people in the United States alone suffer from major depressive disorder (MDD). Over 30% do not benefit from currently available antidepressants and are diagnosed with TRD. TRD remains a highly unmet medical need indication as there are few approved pharmacological agents for TRD and overall, outcomes remain poor. It represents a breakthrough in using precision medicine for CNS diseases. Post this Liafensine is a first–in–class triple reuptake inhibitor targeting transporters for serotonin, norepinephrine, and dopamine. Using its unique big data based Denovo Genomic Marker (DGM™) biomarker platform, Denovo discovered a novel genetic biomarker, termed DGM4™, which was hypothesized to predict liafensine's efficacy in TRD patients. ENLIGHTEN, a DGM4 biomarker–guided, randomized, double–blind, placebo–controlled global Phase 2b trial designed to validate the biomarker hypothesis, enrolled 197 patients with TRD. DGM4–positive TRD patients who received liafensine demonstrated highly significant improvements over the 6–week treatment period compared to those who received placebo. The primary endpoint was met: the change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline for liafensine demonstrated a 4.4–point improvement over placebo (p = 0.0056). All secondary endpoints were also met: changes in both the Clinical Global Impressions Scale–Severity (CGI–S) and the Sheehan Disability Scale (SDS) change from baseline for liafensine showed an approximately 36% improvement over placebo; additionally, the Clinical Global Impressions Scale-Improvement (CGI–I) was 2.3 for liafensine, a 0.6–point improvement over placebo (p = 0.0026). Liafensine was well tolerated and demonstrated an excellent safety profile consistent with previous clinical trials which included more than 2,200 subjects. "I am truly excited about these positive results in TRD, which is one of the toughest central nervous system (CNS) diseases to treat. The results are remarkable as we have seen a greater than 40% improvement in depression symptoms, which is a greater magnitude than some approved drugs in current use." said Matthew Spear, Chief Medical Officer and Chief Development Officer at Denovo. "It also represents a breakthrough in using precision medicine for CNS diseases, as it is the first time a genetic biomarker has been used to enrich responders in TRD patients, which is the key to its benefit." "The success of the ENLIGHTEN trial is a transformative milestone for Denovo as it validates the innovative biomarker approach that Denovo uses to advance otherwise failed late–stage drugs," said Wen Luo, Chief Executive Officer and Chief Scientific Officer of Denovo. "We have started the process of identifying a global partner to expedite further development of liafensine towards the market to benefit millions of TRD patients around the world. We are also working on biomarkers for additional drug candidates in other diseases with high unmet needs. Overall, this marks the beginning of a new era of a more efficient way of developing innovative therapies for CNS diseases." For more information on ENLIGHTEN, visit . About DB104 (liafensine) Liafensine is a first–in–class triple reuptake inhibitor targeting transporters for serotonin, norepinephrine, and dopamine. It was licensed from Albany Molecular Research, Inc. (now Curia) and was previously developed by Bristol–Myers Squibb, who had conducted two large Phase 2b clinical trials in TRD, with a total of more than 2,200 subjects. About Denovo Biopharma Denovo Biopharma LLC is a clinical-stage biopharmaceutical company that uses novel biomarker approaches 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 which are first–in–class drugs with global rights. Visit for additional information. Contact Michael F. Haller, PhD Chief Business Officer and Head of US Finance Denovo Biopharma LLC [email protected] SOURCE Denovo Biopharma LLC