May and June 2026 saw significant clinical and regulatory momentum across nucleic acid therapeutic modalities and strategic activity included a multi-target ASO collaboration between Servier and n-Lorem Foundation in rare neurodevelopmental disorders, and WuXi AppTec’s announcement of a 17% increase in capital expenditure to expand oligonucleotide and peptide manufacturing capacity globally.
Abstract
May and June 2026 saw significant clinical and regulatory momentum across nucleic acid therapeutic modalities. Regulatory highlights included FDA Breakthrough Therapy Designation for Biogen’s intrathecally administered ASO salanersen in spinal muscular atrophy and MHRA authorisation of Moderna and the University of Oxford’s INTERCEPT-Lynch Phase 1/2 trial of mRNA-4194, the first investigational mRNA cancer prevention vaccine. In clinical development, Novartis reported positive Phase 1/2 biomarker data for the AOC del-brax in facioscapulohumeral muscular dystrophy, GSK published Phase 3 data demonstrating a 19% functional cure rate for the ASO bepirovirsen in chronic hepatitis B, and SpliSense secured $13 million from the Cystic Fibrosis Foundation to advance inhaled ASO SPL84 into Phase 2b. Strategic activity included a multi-target ASO collaboration between Servier and n-Lorem Foundation in rare neurodevelopmental disorders, and WuXi AppTec’s announcement of a 17% increase in capital expenditure to expand oligonucleotide and peptide manufacturing capacity globally.
The recent BioE3 policy and Biopharma SHAKTI initiative, with its Rs.10,000/- crore outlay signals a definitive pivot from volume driven growth to value driven innovations in the move to much needed affordable next generation biologics.
July 2026 saw the field push access outward on multiple fronts, from the first FDA approval of a genetic therapy for children as young as 2 years (Vertex’s CASGEVY) to the first international patient treated with satri‑cel, the first CAR‑T therapy approved anywhere for a solid tumor. Regulatory momentum extended across in vivo CAR‑T, allogeneic transplant, and solid tumor cell therapy, while ARPA‑H committed up to $160 million to scalable in vivo gene editing for rare diseases. Alongside these milestones, new partnerships, a €33 million financing, and first patient dosings in pivotal trials for Gaucher disease type 1 and diabetic retinopathy signaled continued investment across the manufacturing, clinical, and commercial landscape.
Abigail Pinchbeck· Cell and Gene Therapy Insigh...· 0 citations
The principles that shape cardiovascular ASO candidate development are discussed, with emphasis on mechanism selection, chemical design, and exposure feasibility, and sequence optimization with exposure-informed target qualification and therapeutic-index engineering throughout ASO candidate selection.
D. Park, Anja Bühler, Christian Schöllhorn et al.· Expert Opinion on Drug Disco...· 0 citations
Primary mitochondrial diseases (PMD) are ultra-rare, genetically diverse disorders that impair cellular energy metabolism and typically present with multisystemic symptoms. Over the past decades, the therapeutic landscape of PMD has evolved substantially. Early trials of non-specific antioxidant and metabolic therapies produced largely negative or mixed results, providing important methodological lessons for the field. More recent studies have adopted improved outcome measures, natural history-informed designs, and precision therapeutic approaches, including gene therapy and nucleoside therapy, which have shown encouraging clinical and regulatory progress. Regulatory agencies have only recently begun approving disease-modifying therapies for selected mitochondrial disorders. The European Medicines Agency (EMA) approved idebenone for Leber Hereditary Optic Neuropathy (LHON) in 2015 but only recently, in 2025 did the Food and Drug Administration (FDA) in the US approve a treatment for Barth syndrome and thymidine kinase 2 deficiency (TK2d). Friedreich’s ataxia received regulatory approval in 2023 from both the EMA and FDA, marking another milestone in mitochondria-related disorders. To comprehensively review clinical and regulatory developments in PMD over the past two decades, we conducted a structured scoping review and horizon scan of published clinical trials and regulatory approvals in PMD from January 2000 to November 2025. Data sources included PubMed, Embase, https://ClinicalTrials.gov, and regulatory agency websites. Recent accelerated and full FDA approvals validate the feasibility of tailored evidence packages, but sustaining this momentum will require more rigorous alignment of trial design with molecular biology, strengthening of natural history infrastructure, deployment of sensitive biomarkers, and adoption of innovative statistical approaches. Early regulatory engagement and robust patient-community partnerships will be key.
A. Karaa, Maria Isabel G. Lopez Sanchez, Claire Stuart et al.· Therapeutic Advances in Rare...· 0 citations
This review summarizes current and emerging model‐informed drug development applications in oligonucleotide therapeutics, with primary emphasis on siRNAs and complementary insights from ASOs.
Paridhi Gupta, Mindy Magee, Vivaswath S. Ayyar· Journal of clinical pharmaco...· 0 citations
Tumor necrosis factor-like ligand 1A (TL1A), encoded by TNFSF15, signals through death receptor 3 on effector T cells, innate lymphoid cells, and intestinal myofibroblasts, driving both chronic intestinal inflammation and tissue fibrosis. In this narrative review, we provide a contemporary appraisal of TL1A-directed therapeutics in inflammatory bowel disease based on electronic searches through May 2026. Three anti-TL1A monoclonal antibodies (tulisokibart, afimkibart, and duvakitug) have advanced to phase 3 trials across multiple global programs, with phase 2 clinical remission rates of 26%-48% in ulcerative colitis (placebo-adjusted differences 15-26 percentage points) and endoscopic response rates of 26%-48% in Crohn's disease, alongside favorable safety profiles. Mucosal transcriptomic and serum proteomic analyses from phase 2 trials, including DDW 2026 readouts from ARTEMIS-UC and TUSCANY-2, provide the first human-tissue confirmation of class antifibrotic activity through the suppression of Th17, myeloid, and extracellular matrix pathways. TNFSF15 risk-variant companion diagnostics are advancing, although their incremental utility remains modest and will be definitively tested in phase 3. The pipeline has expanded to at least 19 development programs, including extended half-life antibodies (XmAb942, SPY002, and BCD-261), bispecifics combining TL1A with IL-23 or α4β7 (RO7837195, XmAb412, LQ080, and ALX001), a first-in-class oral anti-TL1A nanobody, and a first-in-class DR3 receptor antagonist (SL-325). We discuss therapeutic positioning and timing, the opportunity in acute severe UC, and the unusual standing of IBD as the lead indication for this mechanism class. Phase 3 results anticipated in 2026-2027 will be particularly informative for fibrostenotic phenotypes and biologic-refractory patients.
M. Quraishi, V. Jairath, B. Al-Bawardy· Inflammatory Bowel Diseases· 0 citations