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Insights provided by DeciBio, a strategy consultancy focused on the life science and biopharma industry.
Highlights & Summary
March next-generation therapeutics highlighted a broad range of clinical activity across modalities, with particularly strong momentum in gene therapy.
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Cell Therapy
Washington University CAR-T Therapy Receives FDA Breakthrough Therapy Designation for Leukemia | Regulatory
Washington University School of Medicine in St. Louis announced that its investigational CAR-T cell therapy targeting acute lymphoblastic leukemia (ALL) has been granted Breakthrough Therapy designation by the U.S. Food and Drug Administration. The therapy is designed to enhance T-cell persistence and anti-tumor activity, addressing limitations seen in earlier CAR-T approaches, particularly in relapsed or refractory patients. Early clinical data demonstrated encouraging response rates, including durable remissions in a subset of heavily pretreated patients, supporting the designation. Breakthrough Therapy status is intended to accelerate development and regulatory review, reflecting the therapy’s potential to offer meaningful improvement over existing treatments. Investigators noted that the designation will facilitate closer collaboration with the FDA as the program advances through clinical development.
Oryon Cell Therapies Reports Phase 1b/2a Data Demonstrating Motor Improvements in Parkinson’s Disease | Clinical Trial
Oryon Cell Therapies reported interim Phase 1b/2a data from its autologous dopaminergic neuron replacement therapy in Parkinson’s disease, showing early and sustained improvements in motor function. Across the first five treated patients, OFF-state MDS-UPDRS Part III motor scores improved by ~29–62% from baseline at 6–18 months, with additional gains observed in mobility measures and reductions in levodopa use. Neuroimaging (DaT-SPECT) demonstrated increased dopaminergic signaling in the treated brain regions, including a >5-fold increase in one patient, supporting evidence of biological activity. The therapy, derived from patient-specific iPSCs and implanted into the putamen, was well tolerated with no serious adverse events and does not require immunosuppression.
Capricor Therapeutics Presents Phase 3 HOPE-3 Data Showing Functional and Cardiac Benefits in Duchenne Muscular Dystrophy | Clinical Trial
Capricor Therapeutics presented late-breaking Phase 3 HOPE-3 data evaluating deramiocel, an allogeneic cell therapy, in patients with Duchenne muscular dystrophy (DMD), demonstrating statistically significant improvements in both functional outcomes and cardiac measures. The randomized, placebo-controlled trial enrolled 106 patients across 20 U.S. sites, with patients receiving intravenous infusions every three months over a 12-month period. New analyses showed meaningful slowing of disease progression in daily living activities and skeletal muscle function, alongside improvements in cardiac function (e.g., left ventricular ejection fraction), reinforcing prior topline findings. The therapy was generally well tolerated, and the dataset is being used to support an ongoing BLA review with the FDA.
Avaí Bio and Austrianova Initiate GMP Master Cell Bank Production for Klotho-Based Anti-Aging Therapy | Manufacturing
Avaí Bio and Austrianova announced the initiation of GMP-compliant Master Cell Bank (MCB) production for genetically modified cells overexpressing the α-Klotho “longevity protein.” The MCB will serve as the foundational starting material for large-scale manufacturing, enabling the companies’ joint venture, Klothonova, to advance its anti-aging cell therapy program following completion of preparatory activities. These banked cells are intended for use in Austrianova’s Cell-in-a-Box encapsulation platform, supporting a cell-based approach to restoring circulating α-Klotho levels for potential treatment of aging-related diseases such as Alzheimer’s and cancer. Establishing the MCB under GMP standards is expected to improve product consistency, reduce risks such as contamination and genetic instability, and support a scalable, reliable supply chain. Company leadership emphasized this as a key transition into production, noting that MCBs are a prerequisite for downstream manufacturing and long-term clinical development of encapsulated cell therapies.
In Vivo BCMA CAR-T Therapy Demonstrates Early Deep Responses Without Ex Vivo Manufacturing in Multiple Myeloma | Clinical Trial
A Phase 1 study published in Nature Medicine evaluated an in vivo–generated anti-BCMA CAR-T therapy (ESO-T01) in patients with relapsed/refractory multiple myeloma, demonstrating feasibility and early signs of efficacy without the need for leukapheresis, ex vivo manufacturing, or lymphodepleting chemotherapy. The therapy uses an immune-shielded lentiviral vector delivered via a single intravenous infusion to directly reprogram T cells within the patient. Among five heavily pretreated patients (median three prior lines), four achieved objective responses, including three stringent complete remissions, with all evaluable responders achieving minimal residual disease (MRD) negativity by day 60. Safety findings showed no dose-limiting toxicities, though all patients experienced grade ≥3 adverse events, including cytokine release syndrome in four patients (primarily grade 3), which was manageable with standard interventions.
Gene Therapy
Genethon reports two-year functional gains in DMD trial | Clinical Trial
Genethon reported two-year follow-up data from patients treated with GNT0004 showing sustained improvements in motor function and slowed disease progression in boys with Duchenne muscular dystrophy. At the selected dose, treated patients demonstrated gains in NSAA scores, improved performance in timed walking tests, and reductions in muscle damage biomarkers, with no serious safety issues observed. A randomized, placebo-controlled pivotal study is underway to further evaluate the therapy in ambulatory patients.
Ocugen reports 12-month data in geographic atrophy | Clinical Trial
Ocugen reported 12-month Phase 2 data for OCU410 demonstrating a 31% reduction in geographic atrophy lesion growth at the optimal dose compared to control, along with preservation of photoreceptor structure and no treatment-related serious adverse events. The company plans to initiate a Phase 3 trial in 2026 to further evaluate the therapy in patients with dry age-related macular degeneration.
Solid Biosciences doses first patient in SGT-212 trial, raises $240M | Clinical Trial
Solid Biosciences reported initial clinical progress for SGT-212, with the first patient dosed in the Phase 1b FALCON trial for Friedreich’s ataxia and no treatment-related adverse events observed to date. The company also completed a $240 million private placement to support pipeline development, with cash runway expected into the first half of 2028.
Ultragenyx reports Phase 3 data in OTC deficiency | Clinical Trial
Ultragenyx reported Phase 3 data showing that DTX301 led to an 18% reduction in 24-hour plasma ammonia levels compared to placebo, with treated patients maintaining ammonia levels within the normal range through 36 weeks. The therapy was generally well tolerated, and patients were able to reduce use of standard medications and dietary restrictions, with additional follow-up data on treatment burden expected in 2027.
Bayer discontinues ACTUS-101 to prioritize Pompe gene therapy AB-1009 | Clinical Trial
Bayer has discontinued development of its early-stage Pompe disease gene therapy ACTUS-101 after halting enrollment in a Phase 1 study that treated seven patients. The company is prioritizing advancement of its other AAV gene therapy, AB-1009, which has entered a Phase 1/2 trial in the U.S. and received Fast Track and orphan drug designations.
Oligo
Sarepta shares first clinical data for siRNA programs in FSHD1 and DM1 | Clinical Trial
Sarepta reported first clinical data from Phase 1/2 ascending-dose studies of SRP-1001 in facioscapulohumeral muscular dystrophy type 1 (FSHD1) and SRP-1003 in myotonic dystrophy type 1 (DM1), marking the company’s initial clinical readout from its siRNA pipeline. The company said both programs showed dose-dependent muscle exposure, early biomarker effects, and favorable tolerability, with most adverse events described as mild to moderate and not dose dependent. The pipeline is being advanced under an exclusive license with Arrowhead Pharmaceuticals and includes additional siRNA programs in pulmonary and neurodegenerative diseases beyond SRP-1001 and SRP-1003.
Argo hereditary angioedema therapy receives FDA Fast Track | Regulatory
Argo Biopharma announced that the FDA granted Fast Track designation to BW-20805, an investigational siRNA therapy for hereditary angioedema (HAE). BW-20805 targets hepatic prekallikrein mRNA and is intended to provide long-acting prevention of HAE attacks by inhibiting expression of a validated disease target. The company said a global Phase 2 open-label study in adult HAE patients is ongoing, with primary completion expected in the second half of 2026, followed by plans for a global Phase 3 study.
Ribo Highlights RiboPepSTAR Platform for Extrahepatic siRNA Delivery | Manufacturing
Ribo presented new preclinical data on its RiboPepSTAR platform, which is designed to enable targeted siRNA delivery to organs beyond the liver, including the kidney, heart, and adipose tissue. Kidney-directed studies showed selective uptake in proximal tubular cells and up to 80% target knockdown across species from rodents to non-human primates, while a first kidney-targeted drug has entered IND-enabling studies. Ribo also described sustained cardiac knockdown with strong tissue specificity in mouse models and 96% knockdown in adipose tissue in non-human primates.
Aro Biotherapeutics Reports Positive Topline Data for ABX1100 | Clinical Trial
Aro Biotherapeutics reported positive topline Phase 1b results for ABX1100, a muscle-targeted GYS1 siRNA being evaluated as an add-on to enzyme replacement therapy in patients with late-onset Pompe disease. In nine patients followed for 20 weeks, ABX1100 achieved approximately 62% knockdown of GYS1 mRNA in quadriceps muscle through Week 10, with drug and target data at Week 16 supporting the possibility of quarterly or less frequent dosing after the loading regimen. The company also reported an approximately 2.5% mean improvement in forced vital capacity at five months in evaluable patients, alongside reductions in creatine kinase and urinary Hex4 in most patients at Week 10.
Sarepta Moves AMONDYS 45 & VYONDYS 53 Toward Traditional Approval | Regulatory
Sarepta plans to submit supplemental new drug applications by the end of April 2026 seeking conversion of the accelerated approvals for ASO therapies AMONDYS 45 and VYONDYS 53 to traditional approvals following feedback from the FDA. The filings will include data from the Phase 3 ESSENCE confirmatory study, published real-world evidence, and the established safety profiles of both exon-skipping therapies, although the FDA noted that the adequacy of the package for traditional approval will be determined during review. In ESSENCE, numerical trends favored treatment over placebo, but the primary endpoint of 4-step ascend velocity at 96 weeks did not reach statistical significance in the intent-to-treat analysis.
ADCs
Pfizer Cuts Phase 1 ADC From Prior Seagen Acquisition | Commercial
Pfizer has discontinued another early-stage antibody-drug conjugate (ADC) inherited from its $43 billion acquisition of Seagen, underscoring ongoing pipeline pruning within its oncology portfolio. The candidate, PF-08046031 (formerly SGN-CD228A), was in phase 1 testing for solid tumors and targets CD228, a protein expressed on melanoma and other tumor types. Its termination adds to a series of recent cuts affecting Seagen-originated assets, despite earlier indications from Pfizer leadership that major pipeline restructuring was largely complete. The decision reflects Pfizer’s continued prioritization of higher-value programs following its integration of Seagen’s ADC platform. Overall, the move highlights the company’s willingness to cull early-stage ADCs that may not meet evolving strategic or clinical benchmarks within its oncology pipeline.
Bicycle Therapeutics Lays Off 30% of Staff Amidst Underwhelming Phase 2 ADC Results | Personnel
Bicycle Therapeutics is restructuring its pipeline and cutting approximately 30% of its workforce as it deprioritizes its Nectin-4–targeting ADC zelenectide pevedotin, once positioned as a potential challenger to Pfizer’s Padcev in bladder cancer. The decision follows regulatory feedback indicating that the ongoing Phase 2 Duravelo-2 trial is unlikely to support an accelerated approval, despite alignment on dosing strategy, prompting uncertainty around the program’s approval pathway. While zelenectide has shown response rates broadly comparable to existing therapies, including a 58% response in combination with Keytruda in certain patients, analysts view the data as insufficiently competitive relative to Padcev’s higher efficacy benchmarks. The company will continue the trial toward a randomized phase before determining next steps but has already halted other studies and shifted focus away from the asset. Bicycle plans to redirect resources toward other pipeline programs, including an EphA2-targeting ADC and earlier-stage radiopharmaceutical efforts, as part of a strategy to reduce operating costs by about 50% and extend its cash runway into 2030. Overall, the move reflects both regulatory headwinds and competitive pressure in the Nectin-4 ADC space, particularly from entrenched therapies.
BioNTech Advances DualityBio ADC Into Phase 3 Rivaling Merck-Daiichi | Clinical Trial
BioNTech and DualityBio are advancing their B7-H3–targeting antibody-drug conjugate BNT324 (DB-1311) into a phase 3 trial for metastatic castration-resistant prostate cancer, supported by encouraging early clinical data. The pivotal study is designed to enroll approximately 736 patients—about half the size of a competing phase 3 trial from Merck and Daiichi Sankyo evaluating a rival B7-H3 ADC—highlighting a more streamlined development strategy. Both trials will compare their respective ADCs against standard-of-care docetaxel and prednisone, enabling a direct benchmark against existing chemotherapy. The move to late-stage development is underpinned by phase 1/2 results showing a median radiographic progression-free survival of 11.3 months in heavily pretreated patients, including those previously treated with radioligand therapy. By pursuing a smaller, faster trial design, BioNTech and DualityBio aim to accelerate timelines, though this approach may introduce greater statistical and execution risk. Overall, the program positions the partners as a key challenger in the emerging and increasingly competitive B7-H3 ADC landscape.
FDA Grants Fast Track Designation for Ovarian Cancer ADC | Regulatory
The FDA has granted Fast Track designation to Zymeworks’ folate receptor alpha (FRα)-targeting antibody-drug conjugate ZW191 for patients with advanced or metastatic platinum-resistant ovarian cancer, aiming to accelerate its development and review. ZW191 targets FRα, a cell-surface protein highly expressed in multiple tumor types, including a majority of ovarian cancers, supporting its potential applicability across a broad patient population. Notably, the designation was granted irrespective of FRα expression levels, suggesting the therapy could be used without biomarker-based patient selection. The ADC is currently being evaluated in a Phase 1 trial in patients with advanced solid tumors to assess safety, pharmacokinetics, and preliminary antitumor activity. Its design incorporates a topoisomerase I inhibitor payload with potential bystander activity, which may help address tumor heterogeneity. Overall, the Fast Track Designation underscores both the unmet need in platinum-resistant ovarian cancer and continued momentum behind FRα-targeting ADCs in development.
NJ Bio and Aji Biopharma Announce Collaboration for Site-Specific Conjugation Technology | Commercial
NJ Bio and Ajinomoto Bio-Pharma Services have entered into a collaboration to expand access to AJICAP, a site-specific conjugation platform, for discovery-stage and early development antibody-drug conjugate (ADC) programs. The partnership will integrate AJICAP into NJ Bio’s workflows, enhancing its antibody conjugation and linker capabilities and enabling more precise and reproducible attachment of both cytotoxic and non-cytotoxic payloads. The technology allows modification at defined lysine residues without requiring antibody engineering, helping preserve antibody structure while improving pharmacokinetics, therapeutic index, and overall developability. AJICAP is also designed to be scalable and compatible with standard antibody production processes, supporting efficient translation from discovery to development. Through the collaboration, NJ Bio aims to strengthen its position as an end-to-end partner for biopharma companies by combining its expertise in bioconjugation and medicinal chemistry with Ajinomoto’s platform technology. Overall, the partnership highlights continued investment in enabling technologies that can improve ADC design, reduce development risk, and accelerate timelines for next-generation targeted therapeutics.
