Patent Issued for Novel Genetic Biomarker DGM4: Identified Through Liafensine Program for Treatment-Resistant Depression

The United States Patent and Trademark Office has issued patent number 12,612,261, titled “Compositions and methods for assessing the efficacy of inhibitors of neurotransmitter transporters,” for the use of Denovo Biopharma’s DGM4. DGM4 is a novel genetic biomarker discovered through Denovo’s artificial intelligence and big data based Denovo Genomic Marker (DGM) platform for the liafensine (DB104) program for treatment-resistant depression (TRD).¹

“The patent issuance for the DGM4 biomarker represents a significant step in strengthening our DB104 intellectual property portfolio and reinforces our mission to redefine the treatment of TRD, a difficult-to-treat CNS disorder that impacts millions of patients globally,” said Wen Luo, PhD, the chief executive officer of Denovo. “Building on the success of our phase 2b study and Fast Track Designation by the FDA, receiving this patent represents another milestone for DB104 and underscores its potential to transform how we address TRD through a patient-specific, biomarker-driven approach.”

The ANK3 gene, which encodes a scaffolding protein primarily expressed in the nervous system, plays an important role in neuronal signaling through modulation of cell membrane proteins and is linked to psychiatric diseases including bipolar disorder and depression. DGM4 is a completely novel biomarker; it is a single nucleotide polymorphism located within the ANK3 gene discovered by Denovo using the archived samples of patients treated with liafensine. The issuance of this patent provides the DB104 intellectual property portfolio protection until 2043.

Liafensine is a first-in-class triple reuptake inhibitor targeting transporters for serotonin, norepinephrine, and dopamine that is already in phase 3 clinical development. It was licensed from Albany Molecular Research, Inc (now Curia) and was previously in development with Bristol Myers Squibb (BMS) for TRD. BMS conducted 14 clinical trials, which proved the superior safety of liafensine, but ultimately failed to show efficacy in non-biomarker-selected populations with TRD.

Following the discovery of the DGM4 (aka ANK3) biomarker associated with liafensine’s efficacy, Denovo’s ENLIGHTEN phase 2b pivotal trial prospectively demonstrated robust efficacy and a favorable safety profile of liafensine in ANK3-positive patients with TRD. Participants were randomly assigned 1:1:1 to once-daily oral liafensine 1 mg; once-daily oral liafensine 2 mg; or oral placebo once daily. The primary outcome was the Montgomery-Åsberg Depression Rating Scale (MADRS) total score change from baseline to day 42. Of the 189 ANK3-positive participants with TRD who were randomly assigned, 188 of them received study drug and 186 of them had at least 1 dose of study drug and 1 postrandomization efficacy evaluation. The mean MADRS score change in these participants was −15.4 (0.9) for liafensine (including both 1- and 2-mg doses) compared with −11.0 (1.3) for placebo (P = .006). Statistically significant improvements were also seen in all secondary end points. As to safety profile, adverse events were tolerable and there were low rates of meaningful events. Adverse events leading to discontinuation of treatment occurred in 5 participants (4.0%) receiving liafensine and 9 (14.1%) receiving placebo. Overall, liafensine was efficacious and well tolerated in those who were ANK3-positive and had TRD, with clinically meaningful and statistically significant improvements over placebo, thus suggesting ANK3 is viable as a predictive genetic biomarker for liafensine. The results of ENLIGHTEN trial was published in JAMA Psychiatry.²

References

1. Denovo announces issuance of U.S. patent of novel genetic biomarker ANK3 (DGM4™) for liafensine (DB104). News release. April 29, 2026. Accessed April 29, 2026. https://www.globenewswire.com/news-release/2026/04/29/3283625/0/en/denovo-announces-issuance-of-u-s-patent-of-novel-genetic-biomarker-ank3-dgm4-for-liafensine-db104.html

2. Wang G, Aguado M, Spear MA, et al. ANK3 as a novel genetic biomarker for liafensine in treatment-resistant depression: the ENLIGHTEN randomized clinical trial. JAMA Psychiatry. 2025;82;(12):1186-1194.