Osteoarthritis, Knee

Data will be featured at the ASGCT 28th Annual MeetingBRISBANE, Calif., May 02, 2025 (GLOBE NEWSWIRE) -- Pacira BioSciences, Inc. (NASDAQ: PCRX), the industry leader in its commitment to deliver innovative, non-opioid pain therapies to transform the lives of patients, today announced an upcoming podium presentation of findings from its Phase 1 study of PCRX-201 (enekinragene inzadenovec), a locally administered gene therapy candidate for osteoarthritis of the knee. The data will be presented at the 28th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) in New Orleans on May 15. The presentation will highlight how preexisting and treatment-induced neutralizing antibodies (NAbs) impact the therapy’s efficacy, safety, and redosing potential. Presentation Title: Understanding the Clinical Immunogenicity of Locally Injected HCAd Vector Provides Insight into Optimizing Dosing Strategy Presented By: MiJeong Kim, PhD, Senior Director of Translational Sciences at Pacira BioSciences Date and Time: Thursday, May 15 from 2:15–2:30 PM CT, during the “Immunogenicity/NAb Titers” oral session at ASGCT 2025 Pacira will also host a symposium on HCAd for common diseases, like osteoarthritis. Symposium Title: High-Capacity Adenoviral Vectors: Advancing Gene Therapy Beyond AAV to Deliver Cost-Effective Therapies for Common Diseases Speakers: Brendan Lee, Professor of Molecular and Human Genetics, Baylor College of MedicineDerek Jackson, Vice President, Cell & Gene Therapy Product Development at Pacira BioSciencesKilian Guse, Development of Gene Therapy for Musculoskeletal Disorders at Pacira BioSciences Date and Time: Friday, May 16 from 12:15–1:15 PM CT About PCRX-201 (enekinragene inzadenovec)PCRX-201 (enekinragene inzadenovec) features an innovative design based on the company’s proprietary high-capacity adenovirus vector platform. It is currently being studied in the fundamental, underlying chronic inflammatory processes that contribute to “wear and tear” over time in osteoarthritis of the knee, a condition that affects more than 14 million individuals in the U.S. today. In November 2024, Pacira reported promising data from a large Phase 1 study in which PCRX-201 provided sustained improvements in knee pain, stiffness, and function through two years following local administration, with a well-tolerated safety profile. PCRX-201 has received Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. Food and Drug Administration and Advanced Therapy Medicinal Products (ATMP) designation from the European Medicines Agency. PCRX-201 is the first gene therapy to achieve these clinical results and earn these regulatory designations in osteoarthritis of the knee – a testament to its promise and potential. Given the promising Phase 1 results, dosing is underway in a Phase 2 study of PCRX-201 (the ASCEND study) for the treatment of knee osteoarthritis. To learn more about PCRX-201 and the company’s clinical development program, please visit the investor events section of the company’s investor website. About PaciraPacira delivers innovative, non-opioid pain therapies to transform the lives of patients. Pacira has three commercial-stage non-opioid treatments: EXPAREL® (bupivacaine liposome injectable suspension), a long-acting local analgesic currently approved for infiltration, fascial plane block, and as an interscalene brachial plexus nerve block, an adductor canal nerve block, and a sciatic nerve block in the popliteal fossa for postsurgical pain management; ZILRETTA® (triamcinolone acetonide extended-release injectable suspension), an extended-release, intra-articular injection indicated for the management of osteoarthritis knee pain; and iovera®º, a novel, handheld device for delivering immediate, long-acting, drug-free pain control using precise, controlled doses of cold temperature to a targeted nerve. The Company is also advancing the development of PCRX-201 (enekinragene inzadenovec), a novel, locally administered gene therapy with the potential to treat large prevalent diseases like osteoarthritis. To learn more about Pacira, visit www.pacira.com. Investor Contact: Susan Mesco, (973) 451-4030 susan.mesco@pacira.com Media Contact: Sara Marino, (973) 370-5430 sara.marino@pacira.com

Multicenter study sponsored by SELNET to evaluate cirtuvivint as a second-line monotherapy in selected sarcoma subtypesSAN DIEGO, May 01, 2025 (GLOBE NEWSWIRE) -- Biosplice Therapeutics, Inc. (“Biosplice”), a clinical-stage biotechnology company pioneering advancements in small molecule inhibition of CDC-like kinases (CLK) and Dual-specificity tyrosine phosphorylation-regulated (DYRK) kinases, today announced that the first patient has been dosed in a Phase 2 clinical trial evaluating cirtuvivint in patients with advanced soft-tissue sarcomas. The multicenter, open-label trial, led by Principal Investigator Dr. Javier Martin Broto, is sponsored by SELNET (Sarcoma European and Latin American Network) and is being conducted at eight clinical sites across Spain. This Investigator Initiated Trial follows a preclinical collaboration and focuses on specific sarcoma subtypes, aiming to assess the safety and efficacy of cirtuvivint as a monotherapy. SELNET elected to sponsor the trial following a comprehensive review of preclinical data, which demonstrated compelling activity of cirtuvivint across multiple soft-tissue sarcoma cell lines and xenograft models that were refractory to other treatments. The “Multicenter, Open-Label Phase 2 Trial of Cirtuvivint as a Second-Line Therapy in Selected Advanced Soft-Tissue Sarcomas" will evaluate cirtuvivint monotherapy in approximately 30 patients whose disease has progressed following initial standard of care. The trial focuses on specific sarcoma subtypes and aims to assess the safety and efficacy of cirtuvivint in this difficult-to-treat patient population. “This trial represents a critical step forward for patients with advanced soft-tissue sarcomas, who currently face limited therapeutic options after first-line treatment,” said Dr. Yusuf Yazici, Chief Medical Officer of Biosplice. “We are grateful to SELNET and the participating investigators for their partnership in evaluating cirtuvivint in this patient population. Cirtuvivint has shown compelling activity in preclinical sarcoma models, and this study is a key milestone in our efforts to bring new therapeutic options to patients with high unmet need.” Soft-tissue sarcomas (STS) are a heterogeneous group of rare cancers originating in connective tissues, and treatment-resistant forms of the disease remain a significant challenge. Biosplice is exploring cirtuvivint’s utility across multiple tumor types based on its unique mechanism of action and encouraging safety and pharmacokinetic profile observed in earlier studies. Additional information about the study can be found on euclinicaltrials.eu, EUCT 2024-511987-10-00. About Biosplice:Biosplice stands at the forefront of research concentrating on the study and regulation of Cdc2-like kinases (CLKs) and dual-specificity tyrosine-regulated kinases (DYRKs). These kinases play pivotal roles in cell cycle regulation, splicing, and neurodevelopment, marking them as critical targets for therapeutic intervention in a range of diseases, including osteoarthritis, cancer, neurological disorders, and diabetes. With a robust chemical platform for kinase inhibition and a deep understanding of kinase signaling pathways, Biosplice leverages cutting-edge technologies to discover and develop highly selective kinase inhibitors. Biosplice’s drugs in clinical development include lorecivivint for knee osteoarthritis (completed Phase 3) and cirtuvivint for numerous cancers, with a broad preclinical pipeline that encompasses Alzheimer’s disease, diabetes and other degenerative conditions. About Cirtuvivint:Cirtuvivint is a small molecule inhibitor of CLK and DYRK kinases, which are increasingly recognized as key drivers of various cancers. By targeting these kinases, cirtuvivint modulates alternative pre-mRNA splicing, which reduces the expression of genes vital for tumor growth, survival, and drug resistance. The compound has shown broad anti-tumor activity across a range of solid and liquid tumors in extensive preclinical studies. Cirtuvivint has also been investigated for the treatment of advanced solid tumors in two clinical trials. The first, SM08502-ONC-01 (NCT03355066), was a first-in-human dose escalation study designed to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics in patients with advanced solid tumors. The second, SM08502-ONC-03 (NCT05084859), was a Phase 1b trial assessing the efficacy of cirtuvivint in combination with standard treatments for patients with advanced castration-resistant prostate cancer, advanced non-small cell lung cancer, and advanced colorectal cancer. A study sponsored by the National Cancer Institute will explore cirtuvivint in Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS). About SELNET: The Sarcoma European and Latin American Network (SELNET) is a transnational consortium committed to improving outcomes for patients with sarcomas through collaboration in clinical research, education, and access to innovation across Europe and Latin America. Learn more at https://www.biosplice.com Corporate Contact: Erich Horsley erich.horsley@biosplice.com

Novartis disclosed the scrapping of LRX712 alongside news that it has stopped development of GIZ943.\n Novartis has done a little spring cleaning, sweeping a phase 2 osteoarthritis prospect and first-in-human radioconjugate out of its pipeline after assessing evidence on the programs.The actions, which Novartis disclosed (PDF) in its first-quarter results, affect LRX712 and GIZ943. LRX712 was the more advanced of the two candidates. The Swiss drugmaker began a phase 2 trial of the asset in patients with knee osteoarthritis in 2020. A spokesperson for Novartis confirmed the removal of the drug candidate from the pipeline and the thinking behind the decision.“Novartis discontinued the clinical development of LRX712, a chondrogenic drug, investigating its impact on osteoarthritis of the knee following an interim analysis of its phase 2 study which ultimately demonstrated a favorable safety profile, but an insufficient effect on knee cartilage,” the spokesperson said.Researchers identified the synthetic small-molecule drug candidate via phenotypic screening. Preclinical tests suggested the molecule could drive cartilage repair without inducing abnormal bone formation. A drug with that profile could give patients an alternative to surgery, which can lead to fibrous or calcified cartilage that is unable to withstand the forces on the knee. LRX712 fell short of the hoped-for profile. News of the LRX712 discontinuation arrived shortly after Novartis terminated a phase 2 trial of another osteoarthritis prospect, QUC398. The drugmaker was studying the ADAMTS-5 inhibitor in osteoarthritis knee pain but pulled the plug after an interim analysis found an “insufficient effect on pain relief.”Novartis disclosed the scrapping of LRX712 alongside news that it has stopped development of GIZ943 in ovarian and lung cancers. GIZ943, also known as [177Lu] Lu-EVS459, is a radioligand therapy that targets cells that express folate receptor alpha (FRα). The spokesperson said Novartis stopped development “based on an assessment of potential benefit-risk from the phase 1 study.”The trial got underway last year. Novartis recently stopped enrollment after recruiting four patients, well short of its target of 96. The study was supposed to determine the recommended dose in an escalation part and then evaluate its effects in an expansion stage.FRα is overexpressed in many cancers, making it a potentially attractive target for radioligand therapies. Kidney toxicity is a long-standing concern, limiting the development of radioligand therapies against the target and helping antibody-drug conjugates become the modality of choice. AbbVie’s Elahere is already approved, and companies including Eisai and Genmab have FRα-directed ADCs in development.