Insights provided by DeciBio, a strategy consultancy focused on the life science and biopharma industry.

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Highlights & Summary

February included a plethora of clinical trial and regulatory activity across the next-generation therapeutics landscape.

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Cell Therapy

Lilly Acquires Orna Therapeutics to Advance In Vivo Cell Therapy Platform | M&A

Eli Lilly announced plans to acquire Orna Therapeutics to strengthen its position in next-generation cell and gene therapies, particularly in vivo approaches. Orna’s platform leverages circular RNA and lipid nanoparticle (LNP) delivery to enable in-body cell engineering, including potential in vivo CAR-T applications that could bypass complex ex vivo manufacturing. Lilly expects the acquisition to expand its genetic medicines pipeline and accelerate development of more scalable and accessible cell therapies. Orna will continue advancing its pipeline programs while integrating its technology platform into Lilly’s broader R&D infrastructure. The transaction underscores growing pharma interest in in vivo cell therapy modalities designed to simplify manufacturing and improve patient access.

Lyell Initiates First Patient Dosing in Phase 3 Head-to-Head Ronde-cel Trial in LBCL | Clinical Trial

Lyell Immunopharma announced that the first patient has been dosed in the Phase 3 PiNACLE–H2H study evaluating rondecabtagene autoleucel (ronde-cel) in relapsed or refractory large B-cell lymphoma. The randomized trial will compare the dual-targeting CD19/CD20 CAR-T candidate against investigator’s choice of approved CD19 CAR-T therapies (liso-cel or axi-cel) in the second-line setting and plans to enroll approximately 400 patients. The study’s primary endpoint is event-free survival, with patients in the experimental arm receiving a dose of 100 million CAR-T cells. Lyell noted that the parallel single-arm PiNACLE trial in later-line disease remains ongoing, with a BLA submission anticipated in 2027. Company leadership characterized the study as the first randomized head-to-head CAR-T trial intended to generate comparative efficacy data in this setting.

MD Anderson Reports First-in-Human Data for RB-1355 in Advanced Lymphoma | Clinical Trial

Researchers at MD Anderson Cancer Center reported early results from a first-in-human study evaluating RB-1355 in patients with relapsed or refractory non-Hodgkin lymphoma. The novel immune cell therapy was described as safe and well tolerated, with early signs of antitumor activity observed in heavily pretreated patients, including those who had progressed after CAR-T therapy. RB-1355 is designed to be manufactured in approximately one week and does not require lymphodepleting chemotherapy or tumor mutation matching, potentially simplifying treatment logistics. Investigators also reported favorable immune changes within the tumor microenvironment following treatment. The findings suggest the approach may offer a more accessible alternative to traditional cell therapies pending further clinical validation.

Cellares and University of Wisconsin Expand Partnership to Clinical Manufacturing of CRISPR-Edited GD2 CAR-T | Manufacturing

Cellares and the University of Wisconsin School of Medicine and Public Health expanded their collaboration to support clinical manufacturing and regulatory advancement of the university’s CRISPR-edited GD2 CAR-T therapy for solid tumors. The program, initially focused on high-grade gliomas with potential expansion into neuroblastoma, osteosarcoma, and melanoma, will leverage Cellares’ Cell Shuttle automated manufacturing platform and Cell Q automated QC system. Cellares will also provide regulatory support for preparation of the IND submission, including contributions to the CMC section, while UW retains ownership of the filing. The partnership builds on earlier automation work that demonstrated strong manufacturing performance and aims to improve process reproducibility and scalability for gene-edited CAR-T production. Company leadership emphasized that automated manufacturing could shorten the timeline from academic discovery to clinical evaluation.

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Gene Therapy

Ultragenyx gene therapy BLA accepted with Priority Review for GSDIa | Regulatory

Ultragenyx announced that the FDA has accepted its Biologics License Application for DTX401, an AAV gene therapy for Glycogen Storage Disease Type Ia, and granted Priority Review with a PDUFA decision date of August 23, 2026. The submission is supported by data from 52 treated patients, including Phase 3 results showing reduced cornstarch dependence and improved metabolic control with an acceptable safety profile. If approved, DTX401 would be the first therapy targeting the underlying cause of GSDIa and will be manufactured at Ultragenyx’s U.S. gene therapy facility.

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Siren receives Fast Track designation for SRN-101 glioma therapy | Regulatory

Siren Biotechnology said the FDA granted Fast Track designation to SRN-101, its AAV-based immuno-gene therapy for recurrent high-grade glioma. The designation follows recent IND clearance and is intended to support expedited development and regulatory review. SRN-101 is designed to deliver an engineered cytokine locally within tumors to stimulate anti-tumor immune activity, with first-in-human clinical evaluation planned.

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Neurogene’s NGN-401 gains FDA Breakthrough Therapy designation in Rett syndrome | Regulatory

Neurogene announced that the FDA granted Breakthrough Therapy designation to NGN-401, a gene therapy candidate for Rett syndrome, based on interim Phase 1/2 efficacy and safety data. The designation is intended to accelerate development and review and follows prior RMAT and Rare Pediatric Disease designations. NGN-401 is being evaluated as a one-time MECP2 gene therapy in the registrational Embolden trial, with dosing completion expected in mid-2026.

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4DMT completes enrollment in Phase 3 wet AMD trial of 4D-150 | Clinical Trial

4D Molecular Therapeutics reported completion of enrollment in the Phase 3 4FRONT-1 trial evaluating 4D-150 in treatment-naïve wet age-related macular degeneration patients. The randomized study compares intravitreal 4D-150 with aflibercept and will assess visual acuity outcomes and reduction in injection burden, with topline data expected in the first half of 2027. Enrollment for the global companion Phase 3 trial, 4FRONT-2, remains ongoing with completion anticipated in late 2026.

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Opus Genetics raises $25M in private placement financing | Financing

Opus Genetics announced a $25 million private placement through the sale of Series B non-voting convertible preferred stock, led by Adage Capital Management with participation from Trails Edge Capital Partners and Marshall Wace. The proceeds will support advancement of the company’s gene therapy programs and general corporate operations, with the company projecting cash runway into the first half of 2028. The financing is expected to close on February 18, 2026, subject to customary conditions.

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Oligo

GSK and Frontier Biotechnologies Sign up to $1B siRNA Licensing Deal | Partnership

GSK has entered an exclusive global licensing agreement with Frontier Biotechnologies to develop, manufacture, and commercialize two siRNA candidates, one at IND stage and one in preclinical development. Frontier will receive $40 million upfront and is eligible for up to $963 million in development, regulatory, and commercial milestone payments, plus tiered royalties on worldwide net sales. The deal strengthens GSK’s immunology pipeline with oligonucleotide therapies that may address multiple kidney disease indications.

Ribo and RiboCure Ink up to $4.4B Global siRNA Licensing Agreement with Madrigal for MASH | Partnership

Madrigal Pharmaceuticals has secured an exclusive global license to six preclinical siRNA programs from Ribo and RiboCure for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). Madrigal will pay $60 million upfront, while Ribo could receive up to $4.4 billion in development, regulatory, and commercial milestone payments, plus royalties on future product sales. The collaboration expands Madrigal’s MASH pipeline beyond small molecules by adding RNA-based gene-silencing approaches built on Ribo’s GalSTAR platform.

Aro Biotherapeutics Reports Early Efficacy for siRNA asset for Pompe Disease | Clinical Trial

Aro Biotherapeutics announced preliminary Phase 1b data showing that ABX1100, a muscle-targeted GYS1 siRNA, produced strong and sustained biological activity in adults with late‑onset Pompe disease (LOPD). The investigational therapy uses a CD71-targeted Centyrin-siRNA conjugate to reduce GYS1 expression in muscle, aiming to lower glycogen synthesis as a substrate reduction strategy. Early results indicate favorable pharmacokinetics, robust GYS1 mRNA knockdown, and biomarker improvements, supporting advancement of ABX1100 as a potential complement or alternative to enzyme replacement therapy.

FDA Reverses Decision and Will Review Moderna’s mRNA Flu Vaccine | Regulatory

The FDA has reversed an earlier refusal-to-file decision and will now review Moderna’s application for its first mRNA-based seasonal influenza vaccine. The agency initially declined to accept the filing over concerns about the adequacy of clinical trial data but agreed to proceed with review after a follow-up Type A meeting and modifications to the submission. The decision could pave the way for a new mRNA flu option later this year, though it comes amid broader political scrutiny of vaccine regulation under the current administration.

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FDA Accepts Olezarsen sNDA for Priority Review in Severe Hypertriglyceridemia | Regulatory

Ionis Pharmaceuticals announced that the FDA has accepted its supplemental New Drug Application for olezarsen for the treatment of severe hypertriglyceridemia (sHTG) and granted Priority Review, setting a PDUFA date of June 30, 2026. The submission is supported by Phase 3 CORE and CORE2 trials, where olezarsen achieved up to a 72% placebo-adjusted reduction in triglycerides, an 85% reduction in acute pancreatitis events, and brought nearly 90% of patients below the 500 mg/dL risk threshold. If approved, the APOC3‑targeting antisense therapy could offer a disease‑modifying option for the roughly 3 million U.S. patients with sHTG, including over 1 million at particularly high risk of pancreatitis.

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ADCs

Daiichi Cuts Next Generation ADC From Pipeline | Commercial

Daiichi Sankyo has removed its next-generation claudin-6-targeting ADC DS-9606 from its development pipeline following a portfolio review, despite internal validation of its utility in germ cell tumors and perceived potential for further development in that setting. The company framed the discontinuation as part of a broader strategy to prioritize late-stage oncology assets and those with the greatest projected impact. DS-9606 was intended to be the first in a series of ADCs using Daiichi Sankyo’s modified pyrrolobenzodiazepine (mPBD) DNA-targeting payload, and leadership emphasized that the decision does not signal an end to the mPBD ADC platform, which will continue with other targets and carrier antibodies. In parallel, the firm reported a delay for the Phase III Avanzar trial of Datroway plus Imfinzi in first-line NSCLC, pushing the anticipated data readout from late 2025 into the second half of this year. Daiichi Sankyo and AstraZeneca have also been refining Datroway’s positioning, responding to mixed Phase III results by incorporating a TROP2-based AI biomarker in NSCLC and adjusting regulatory strategy, including withdrawing and refiling applications to focus on populations where the ADC has already demonstrated benefit.

Iza-Bren Delivers Positive Phase III Interim Results in TNBC | Clinical Trial

SystImmune and Bristol Myers Squibb reported that izalontamab brengitecan (iza-bren), an EGFR×HER3 bispecific antibody-drug conjugate, achieved positive topline results in the Phase III BL-B01D1-307 trial in patients with previously treated unresectable locally advanced or metastatic triple-negative breast cancer whose disease had progressed after prior taxane therapy. In a prespecified interim analysis, iza-bren met its dual primary endpoints, showing statistically significant and clinically meaningful improvements in progression-free survival and overall survival compared with physician’s choice chemotherapy. These data represent the third Phase III study in which iza-bren has achieved its primary endpoint(s) and mark the first time a bispecific ADC in triple-negative breast cancer has reported positive results for both progression-free and overall survival in a Phase III trial. Leaders from Biokin and Bristol Myers Squibb highlighted the urgent need for better options in advanced triple-negative breast cancer and stated that these findings reinforce confidence in iza-bren’s potential to deliver meaningful clinical benefit across multiple cancers and to change outcomes in hard-to-treat tumors through EGFR/HER3-targeted bispecific ADC technology. The BL-B01D1-307 study is sponsored by Biokin in mainland China, with SystImmune and Bristol Myers Squibb collaborating on iza-bren’s development outside China under an exclusive licensing agreement, and full results are planned for presentation at an upcoming medical conference.

WuXi XDC Enters Collaboration With Earendil Labs For Payload-Linker Technology Platform | Partnership

WuXi XDC has entered a strategic collaboration with Earendil Labs, granting Earendil an exclusive global license to its proprietary WuXiTecan-2 payload-linker technology for multiple specific targets, with a total potential deal value of up to approximately $885 million including upfront, development, regulatory, and sales milestone payments, plus tiered royalties on net sales of any commercialized ADCs. Earendil will use WuXiTecan-2 to conjugate mono- and bispecific antibodies discovered via its AI-driven platform and advance ADC candidates, while WuXi XDC will provide integrated CRDMO support, including CMC development and manufacturing of ADC components . The partners describe this as a robust strategic alliance that combines WuXi XDC’s globally recognized ADC technology and end-to-end services with Earendil’s differentiated AI-enabled antibody discovery to accelerate next-generation ADC development and address significant unmet medical needs in cancer, autoimmune, and other diseases. Leadership from both companies highlight the collaboration as a milestone that validates WuXiTecan-2’s platform value and represents a powerful convergence of frontier AI with a world-leading ADC CRDMO, aiming to improve success rates, speed development, and bring more effective and safer ADCs to patients worldwide. WuXi XDC positions this deal as another significant step in empowering cutting-edge innovation for partners, while Earendil underscores how the technology integration is intended to streamline biopharmaceutical R&D and support the high-quality growth of its rich pipeline of bispecific and multi-specific ADCs.

Promatix Biosciences Presents Positive Preclinical Data For First-In-Class Bispecific ADC | Clinical Trial

Promatix Biosciences presented positive preclinical data at the 16th World ADC London Summit for PBS293-MMAE, a first-in-class EGFR×EphA2 cis-bispecific ADC developed using its proteomics-based platform to enable dual-antigen “AND-gate” targeting and improve tumor selectivity. Proteomic and FACS analyses of patient-derived colon cancer xenografts demonstrated high membrane co-localization of EGFR and EphA2, supporting the biological rationale for dual engagement, and multiple studies confirmed that PBS293 requires both antigens for binding, internalization, and cytotoxicity via hybrid avidity. In KRAS-mutant HCT116 colorectal cancer cells, PBS293-MMAE showed low-nanomolar potency more than 50-fold greater than cetuximab-MMAE and delivered significantly higher, dose-dependent tumor growth inhibition and sustained tumor suppression in xenograft models. The ADC also demonstrated substantially lower cytotoxicity in normal human keratinocytes compared with cetuximab-MMAE, further supporting its potential to enhance efficacy while reducing on-target off-tumor toxicity such as skin effects. PBS293-MMAE is being developed for advanced colorectal cancer with the goal of addressing a major unmet need beyond the roughly 15% of patients who benefit from current EGFR-targeted monoclonal antibodies, and Promatix is building a broader pipeline of bispecific ADCs across colorectal and other solid tumors using its TxPro/CipherPro/AviPro/BiPro platform stack.

Avacta Therapeutics Demonstrates Favorable Payload Delivery Compared to Enhertu | Clinical Trial

Avacta reported new preclinical data showing that its pre|CISION FAP-Exd (AVA6103) mechanism delivers a more favorable tumor-targeting profile than the marketed ADC Enhertu (trastuzumab deruxtecan, T-Dxd), using an AI-generated synthetic comparator arm based on published AstraZeneca nonclinical data. The analysis in a FAP-high animal model indicates three pharmacokinetic advantages for FAP-Exd versus T-Dxd: more rapid drug penetration into the tumor with tumor Cmax reached within minutes rather than 24 hours,, and a nearly three-fold higher Tumor Selectivity Index over 14 days. Avacta’s scientists also observed higher activity of FAP-Exd in tumor models with the lowest FAP expression compared with variable activity of T-Dxd at low HER2 expression levels, along with deep, durable responses persisting for many weeks after a three-dose regimen. CEO Christina Coughlin said this data suggests pre|CISION may offer important advantages over ADC mechanisms, potentially improving both safety and effectiveness by delivering more payload selectively to tumors. Avacta expects to initiate a Phase 1 clinical trial of AVA6103 in the first quarter of 2026 and plans to present the dataset at an upcoming scientific congress and submit it for peer-reviewed publication.