Fabry disease is a lysosomal storage disease tied to the X chromosome and caused by pathogenic variants in the GLA gene encoding galactosidase A. It is characterized by progressive accumulation of galactosidase A substrates, including Gb3 and lyso-Gb3, mainly in the kidney, heart and nervous system.

AAV-based therapies for Duchenne muscular dystrophy (DMD) have shown efficacy, but have limitations such as poor delivery to target tissues and toxicity associated with the vector. Gemma Biotherapeutics Inc. has developed a gene therapy candidate, GB-703, which uses a new myotropic, integrin-binding AAV capsid containing a codon-optimized, deimmunized hybrid payload.

Defects in antigen presentation lead to resistance to cancer immunotherapy, where type I conventional dendritic cells (cDC1s) are crucial drivers of antitumor immunity and their presence is tied to favorable responses and better outcomes. Intratumoral delivery of adenoviral vector, Ad5-PIB, encoding PU.1, IRF8 and BATF3 reprograms tumor cells into cDC1-like antigen-presenting cells and has shown synergy with immune checkpoint blockade (ICB) therapy at exerting antitumor immunity. Asgard Therapeutics AB has developed AT-108, a lead candidate developed for durable efficacy.

Umoja Biopharma Inc. performed preclinical studies to evaluate the antitumor activity of UB-VV500, an off-the-shell lentiviral vector CAR T-cell product. It is based on its Vivovec technology and designed to engineer fully human anti-B-cell maturation antigen (BCMA)/G protein-coupled receptor class C group 5 member D (GPRC5D) dual-targeting chimeric antigen receptor (CAR) T cells, for the potential treatment of multiple myeloma (MM).

Sangamo Therapeutics Inc. discussed gene regulation approaches for neurodegenerative diseases when presenting findings on their clinical candidate ST-506 for the treatment of prion disease.

Pancreatic ductal adenocarcinoma (PDAC) is still a highly lethal cancer with limited therapeutic options. Its lethality mainly stems from activating KRAS mutations and a metabolic dependence on nicotinamide adenine dinucleotide (NAD). Researchers from Remedy Plan Inc. have presented data on RPT-E-037, which exerts dual targeting of NAD metabolism through Nampt inhibition and KRAS signaling inhibition using a pan-RAS inhibitor (RMC-6236).

Recludix Pharma Inc. recently presented data on their new STAT1/3 inhibitors REX-6553 and REX-6547 for treating dermatological inflammatory skin diseases.

A new strategy aims to improve gene therapy for Pompe disease by optimizing both the genetic component that restores the function of a deficient lysosomal enzyme and the vector that delivers it to the target tissue while avoiding the liver. The findings suggest that combining an optimized transgene with a targeted capsid could significantly enhance the effectiveness of gene therapy for Pompe disease.

Antibody-drug conjugates (ADCs) with a dual payload, which deliver two distinct cytotoxic agents via a single antibody, are emerging therapeutics developed to address the limitations of classic ADCs. Primelink Biotherapeutics (Shenzhen) Co. Ltd. recently presented data for their dual-payload ADCs, highlighting PLB-015, which carries a TOP1 inhibitor and an ATR inhibitor with an anti-HER2 antibody and is designed to inhibit the DNA damage response activated by cancer cells when harmed.