Denovo Biopharma to Present Positive Phase 2b ENLIGHTEN Trial Data for DB104 in Treatment-Resistant Depression at ASCP 2024

Denovo Biopharma LLC, based in San Diego, has revealed promising findings from its Phase 2b clinical trial named ENLIGHTEN, evaluating the drug DB104 (liafensine) for patients suffering from treatment-resistant depression (TRD). These results will be presented at the American Society of Clinical Psychopharmacology (ASCP) Annual Meeting in Miami, FL.

The trial's positive outcomes will be featured in two sessions at the ASCP meeting. An oral presentation, titled "Use of Biomarkers to Identify Treatments for Psychiatric Patients: The Right Medicine for the Right Patient at the Right Time," will be chaired by Larry Alphs, MD, PhD, on May 30. Additionally, a poster presentation titled "Use of a Novel Pharmacogenomic Biomarker to Enrich Responders for Liafensine in Treatment-Resistant Depression Patients in a Phase 2b Clinical Study" will be conducted by Matt Spear, MD, on May 29.

Matthew A. Spear, MD, the Chief Medical Officer of Denovo Biopharma, expressed delight over the detailed positive data from the ENLIGHTEN trial, marking the first time such evidence has been presented for TRD. The trial successfully met its primary and secondary endpoints, showcasing the effectiveness of Denovo's genetic biomarker discovery platform, DGM4. The platform aided in the patient selection process, indicating that liafensine might offer much-needed therapeutic options for TRD—a condition with a significant unmet medical need. Dr. Spear highlighted that this is the first instance where a genetic biomarker has been employed to identify and choose suitable patients for psychiatric treatment. This innovation could potentially allow clinicians to determine the appropriate treatment for patients through simple blood or buccal swab tests in a clinical setting.

The ENLIGHTEN Phase 2b clinical study was a DGM4 biomarker-guided, randomized, double-blind, placebo-controlled global trial aimed at validating the biomarker hypothesis. The trial enrolled 197 patients with TRD. DGM4-positive TRD patients treated with liafensine showed significant improvements during the 6-week treatment period compared to those who received a placebo. The primary endpoint was achieved, with a 4.4-point improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline for liafensine over placebo. Secondary endpoints were also met, with approximately 36% improvement in both the Clinical Global Impressions Scale-Severity (CGI-S) and the Sheehan Disability Scale (SDS) change from baseline for liafensine over placebo. Additionally, the Clinical Global Impressions Scale-Improvement (CGI-I) was 2.3 for liafensine, a 0.6-point improvement over placebo. Liafensine was well-tolerated, maintaining an excellent safety profile consistent with previous clinical trials involving over 2,200 subjects.

TRD is a condition affecting over 23 million people in the U.S., with more than 30% of major depressive disorder (MDD) patients not responding to existing antidepressants. This represents a significant unmet medical need as there are limited approved treatments and poor overall outcomes for TRD.

Liafensine is a first-in-class triple reuptake inhibitor targeting serotonin, norepinephrine, and dopamine transporters. Initially licensed from Albany Molecular Research, Inc. (now Curia), and previously developed by Bristol-Myers Squibb, liafensine has undergone extensive Phase 2b clinical trials in TRD, involving over 2,200 subjects. Denovo's unique AI and whole genome sequencing-based Denovo Genomic Marker (DGM) biomarker platform enabled the discovery of the novel genetic biomarker, DGM4. The ENLIGHTEN study supports the predictive capability of the DGM4 biomarker for liafensine's efficacy in TRD patients.

Denovo Biopharma is a clinical-stage biopharmaceutical company that leverages novel biomarker approaches to conduct efficient clinical trials in targeted patient subpopulations, thereby increasing the likelihood of success. The company has eight late-stage drugs in its pipeline, addressing significant unmet needs in oncology and central nervous system diseases, most of which are first-in-class drugs with global rights.