Ultragenyx Submits Rolling BLA for DTX401 Gene Therapy with Nearly 2-Year Durability Data; VantAI and Halda Launch $1B+ RIPTAC Collaboration

Long-lasting efficacy for nearly 2 years!Gene Therapy Submits Rolling Application to FDA for Market Approval

Ultragenyx Pharmaceutical recently announced that it has submitted a rolling Biologics License Application (BLA) to the U.S. FDA for its AAV gene therapy DTX401, intended for the treatment of Glycogen Storage Disease Type Ia (GSDIa). The company has submitted the non-clinical and clinical modules to the FDA and plans to complete the full application, including the Chemistry, Manufacturing, and Controls (CMC) module, by the fourth quarter of 2025 to expedite the review process for this therapy.

DTX401 is an investigational AAV8 gene therapy aimed at stably expressing active G6Pase-α under the control of a natural promoter., enabling the treated liver cells to respond to normal hormonal signals that regulate glucose, including insulin, glucagon, and cortisol. The BLA submission includes the previously announced 96-week data from a Phase 3 randomized, placebo-controlled trial. The study results showed that, compared to baseline,Patients treated with DTX401 further reduced their daily cornstarch intake at the last follow-up: the continuous DTX401 treatment group showed a 60% decrease, while the placebo-to-DTX401 treatment group exhibited a 64% reduction, both representing significant improvements compared to the data at 48 weeks.This result further confirms the lasting efficacy of DTX401 in alleviating patients' metabolic burden.

Over $1 Billion! Proxima's Development Collaboration for Novel Bispecific Molecules

VantAI and Halda Therapeutics today announced a strategic collaboration potentially exceeding 1 billion U.S. dollars.Aimed at jointly promoting the research and development of novel Regulated Induced Proximity Targeting Chimeras (RIPTAC) therapies for cancer and immune-related diseases.Both parties will fully integrate their respective core technical advantages to establish a long-term cooperation pathway, in order to accelerate the discovery and clinical development of selective proximity-based therapies.

Under this collaboration framework, VantAI will utilize its Neo-1 foundational model and NeoLink high-throughput structural proteomics platform to rapidly identify and validate context-specific target-effector combinations. These identified combinations will be directly integrated into Halda's self-developed RIPTAC pipeline, a platform that achieves precise selective action on disease-related cells through a unique "hold-and-kill" mechanism. The collaboration between the two parties deeply integrates AI-driven rational drug design with clinically validated innovative mechanisms, potentially bringing a new generation of selective therapies to the fields of oncology and immunology.

Successful Restoration of Functional Protein Levels! Positive Results of Individualized Antisense Oligonucleotide Therapy Announced

n-Lorem Foundation announced today that its latest research findings have been published inNucleic Acids Research，This study systematically analyzed glycogen branching enzyme (GBE1) Pathogenic intronic splicing variants of the gene and discovered an antisense oligonucleotide (ASO) that can regulate splicing, restoring the expression of functional GBE1 protein in cells from patients with Adult Polyglucosan Body Disease (APBD).. The study focuses on four individuals carrying the sameGBE1APBD patients with deep intronic deletion-insertion mutations, which lead to the formation of abnormal splice sites and generate unstable truncated proteins, thereby disrupting glycogen synthesis and causing abnormal accumulation, ultimately resulting in cumulative damage to nerves and organs.

Using long-read sequencing technology, the research team confirmed that all four patients carried the same pathogenic mutation, a finding which means that all patients could potentially be treated with the same ASO therapy. In subsequent high-throughput cell screening experiments, scientists successfully identified ASO candidate molecules capable of effectively blocking the aberrant splice site and significantly increased the levels of functional GBE1 enzyme in patient cells, validating the feasibility of reducing glycogen accumulation by enhancing enzyme activity.Since the mutation isGBE1The second most common mutation in the gene, this research achievement not only provides a personalized treatment pathway for extremely rare patients but also explores new potential solutions for a broader group of APBD patients.

References:

[1] VantAI and Halda Therapeutics Forge Alliance to Discover Next-Generation RIPTAC Medicines. Retrieved August 19, 2025 from https://www.businesswire.com/news/home/20250819757409/en/VantAI-and-Halda-Therapeutics-Forge-Alliance-to-Discover-Next-Generation-RIPTAC-Medicines

[2] Ultragenyx Initiates Rolling Submission of Biologics License Application (BLA) to U.S. FDA for DTX401 AAV Gene Therapy for the Treatment of Glycogen Storage Disease Type Ia (GSDIa). Retrieved August 19, 2025 from https://www.globenewswire.com/news-release/2025/08/18/3134959/0/en/Ultragenyx-Initiates-Rolling-Submission-of-Biologics-License-Application-BLA-to-U-S-FDA-for-DTX401-AAV-Gene-Therapy-for-the-Treatment-of-Glycogen-Storage-Disease-Type-Ia-GSDIa.html

[3] n-Lorem Foundation Publishes Study Showing Targeted ASO Therapy Restores GBE1 Protein in APBD Patient Cells. Retrieved August 19, 2025 from https://www.businesswire.com/news/home/20250819544430/en/n-Lorem-Foundation-Publishes-Study-Showing-Targeted-ASO-Therapy-Restores-GBE1-Protein-in-APBD-Patient-Cells