Adstiladrin (nadofaragene firadenovec-vncg) / Ferring, FKD Therapies, Royalty - LARVOL DELTA

SYMP-27: LUNAR: Safety and Efficacy Evaluation of Nadofaragene Firadenovec instilled into the Renal Pelvis in Subjects with Low-Grade Upper tract Urothelial Carcinoma – a Single-Arm, Open Label Phase 1/2 Trial (SIU 2025) - No abstract available

Clinical • P1/2 data • Oncology • Solid Tumor • Urothelial Cancer

Novel small molecule inhibitors of mitochondrial permeability transition pore (mPTP) block platelet procoagulant activity (ASH 2025) - "However, traditional therapeutic mPTP inhibitors, such as cyclosporine A, which targetcyclophilin D (CypD), exhibit off-target effects and cytotoxicity, limiting their clinical application. Injury size was comparable between groups.Altogether, our findings support MC63 and TR002 as selective inhibitors of platelet mPTP, andprocoagulant platelet activity, effectively limiting thrombosis without impairing essential hemostaticfunctions. These data highlight pharmacologic mPTP inhibition as a promising approach to saferantithrombotic therapies."

Cardiovascular • Hematological Disorders • Thrombosis • ANXA5 • PPIF • SELP

Intravesical gemcitabine (Inlexzo) for bladder cancer. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Cost-effectiveness Analysis of Treatments for Bacillus Calmette-Guérin-unresponsive Carcinoma in Situ of the Bladder. (PubMed, Eur Urol) - "Current pricing of bladder-sparing treatments poses significant financial barriers for patients with BCG-unresponsive CIS. Gemcitabine/docetaxel is most cost effective when only one therapy line is considered before RC, although this varies by clinical scenario. Upfront RC is most cost effective for patients wanting to try up to two lines of therapy. For patients only willing to try FDA-approved options and unwilling to undergo upfront RC, pembrolizumab is the most cost-effective option. Our findings highlight the need for better treatment selection tools and more equitable pricing."

HEOR • Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Male reproductive and sexual health outcomes following intravesical therapy for non-muscle invasive bladder cancer. (PubMed, World J Urol) - "With fatherhood increasingly occurring beyond age 40, uro-oncologists should consider the potential effects of intravesical therapy on male fertility and sexual function. Expanding research into reproductive outcomes among NMIBC patients may support more informed counseling on this matter."

HEOR • Journal • Review • Bladder Cancer • Genito-urinary Cancer • Infertility • Oncology • Sexual Disorders • Solid Tumor

Systematic study of human adenovirus receptor-usage utilizing a human in vitro respiratory epithelial cell model (ESGCT 2024) - "However, ADSTILADRIN, an interferon expressing replication-deficient recombinant adenovirus type 5 vector (also known as rAd-IFNa/Syn3) is so far the only adenovirus-based gene therapy product amongst the over 30 FDA and EMA approved cellular and gene therapy products...With comparative analysis of previous knowledge and our recent data, we are on the way to build up a clear landscape of the human adenoviruses receptor profile. Our in vitro model with adenovirus major receptor-knockout cell lines will enable the identification of the most applicable adenovirus types for individual therapeutic application and to further understand adenovirus infection biology."

Preclinical • Gene Therapies • Infectious Disease • CD46 • DSG2

Ferring Highlights New Real-World Research with ADSTILADRIN (nadofaragene firadenovec-vncg) in Clinical Practice (Businesswire) - "A Ferring-sponsored study will present baseline characteristics and demographics from the initial patient cohort enrolled in ABLE (ADSTILADRIN in BLadder CancEr)-41, a Phase 4 multicenter non-interventional study examining the use of ADSTILADRIN in a real-world setting. In addition, two independent real-world studies will be presented. This includes a study analyzing electronic billing records for 101 patients from 19 U.S. medical centers who received ADSTILADRIN and is exploring durability of remaining on ADSTILADRIN, and lack of progression to radical cystectomy. A third abstract is a case series evaluating re-induction with ADSTILADRIN among 17 patients across 8 academic and community settings, the findings of which were published recently in The Journal of Urology."

Real-world • Bladder Cancer

Ferring Expands Growing Body of Real-World Evidence Reinforcing Use of ADSTILADRIN (nadofaragene firadenovec-vncg) in Urology Practices (Businesswire) - "The data – presented at the 99th Annual Meeting of the North Central Section of the AUA in Chicago, IL – showed a complete response (CR) rate of 77% (10/13) at 3 months, including 70% in patients with CIS± papillary tumors (7/10) and 100% (3/3) in those with papillary-only lesions....Thirteen patients met entry criteria with a mean age of 77.7 years. Pretreatment pathology showed 10 CIS± papillary tumors and 3 papillary-only lesions. Patients received a median of 12 prior BCG doses (range 6-19). Nadofaragene firadenovec was administered intravesically 75 mL (3×10¹¹ viral particles/mL) and retained for 1 hour. All patients were premedicated with oral vibegron 75 mg, a treatment for overactive bladder and nearly all patients (12/13) retained the medication in their bladder for the full hour."

Real-world evidence • Bladder Cancer

Phase 3 Randomized Study to Evaluate the Efficacy and Safety of Intrapleural Administration of Adenovirus-Delivered Interferon Alpha-2b with Celecoxib and Gemcitabine in Pleural Mesothelioma Patients (IMIG 2025) - "Interferon (IFN) gene transfer with recombinant adenovirus (rAd-IFN) delivers high local IFN-α2b levels when injected into the pleural space, transfecting both mesothelial and tumor cells. Lack of statistical significance may be due to the small underpowered sample size, lowered due to limited enrollment. However, both treatment and control groups had median OS greater than historical controls of gemcitabine alone in second line therapy of PM (Zauderer et al, Lung Cancer, 2014) suggesting possibly biological effect of the celecoxib."

Clinical • P3 data • Gene Therapies • Lung Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Neutropenia • Pleural Mesothelioma • Solid Tumor • IFNA1

Jacob Moyer and Mark Tyson present retrospective data on prophylactic rectal diazepam for intravesical nadofaragene firadenovec administration. (UroToday) - "Results demonstrate significant reductions in bladder spasms and retention failure with 10mg rectal diazepam pretreatment compared to other or no prophylaxis, translating to absolute reductions of 24-25% or relative reductions approaching 70%. Only 4% of diazepam-pretreated patients experienced medication loss versus 29% without, critically important given nadofaragene's quarterly dosing schedule."

Retrospective data • Bladder Cancer

ABLE-32: Trial of Nadofaragene Firadenovec vs. Observation in Participants With Intermediate Risk Non-Muscle Invasive Bladder Cancer (clinicaltrials.gov) - P3 | N=454 | Recruiting | Sponsor: Ferring Pharmaceuticals | Trial completion date: Mar 2030 ➔ Jun 2031 | Trial primary completion date: Mar 2030 ➔ Jun 2028

Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Mechanisms, Clinical Trials, and New Treatments for BCG-Unresponsive in Nonmuscle Invasive Bladder Cancer. (PubMed, Cancer Med) - "The treatment landscape for BCG-unresponsive NMIBC is rapidly evolving, with immune checkpoint inhibitors, gene therapies, targeted agents, and advanced drug delivery systems showing promising efficacy. These innovations provide bladder-preserving options for patients ineligible for radical cystectomy. Future directions include biomarker-driven therapy selection, combination regimens, and optimized intravesical delivery platforms to improve long-term outcomes."

IO biomarker • Journal • Review • Bladder Cancer • Gene Therapies • Genito-urinary Cancer • Oncology • Solid Tumor

TR-002 for the Treatment of Advanced, Unresectable or Metastatic Solid Tumors and Unresectable or Metastatic, Refractory Pancreatic Adenocarcinoma (clinicaltrials.gov) - P1 | N=52 | Not yet recruiting | Sponsor: University of California, Davis

New P1 trial • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Gene-mediated therapy for BCG-unresponsive nonmuscle-invasive bladder cancer: mechanisms, clinical evidence, and practical implementation. (PubMed, Curr Opin Urol) - "Gene-mediated therapy is gradually advancing NMIBC care, with expanding indications and potent combinations positing itself to improve bladder preservation and long-term outcomes."

IO biomarker • Journal • Bladder Cancer • Gene Therapies • Genito-urinary Cancer • Oncology • Solid Tumor

INNOVATIONS IN THERAPIES FOR BACILLUS CALMETTE-GUERIN (BCG) FAILURE NON-MUSCLE INVASIVE PATIENTS (PubMed, Harefuah) - "Diverse treatments, both systemic and local, administered directly into the bladder, have been investigated in recent years to mitigate the need for cystectomy. This review article provides an overview of current approved therapeutic options such as combined intravesical chemotherapy with gemcitabine and docetaxel, systemic therapy with pembrolizumab, intravesical therapy with nadofaragene firadenovec, and innovative investigational treatments including TAR-200 drug-releasing supplement therapy and novel viral therapy, cretostimogene grenadenorepvec."

Journal • Review • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Ferring Pharmaceuticals Co., Ltd. announced that the PMDA has accepted the NDA for nadofaragene firadenovec for review, following submission on August 27th, 2025. (Businesswire) - "The NDA for nadofaragene firadenovec is based on results from a Phase 3 trial conducted in Japan."

Japan filing • Bladder Cancer

Advancements in bladder cancer immunotherapy: a focus on intravesical approaches. (PubMed, Front Pharmacol) - "Novel combinations, such as sasanlimab (a PD-1 monoclonal antibody) with BCG, have improved event-free survival in high-risk non-muscle-invasive bladder cancer (NMIBC). Intravesical anti-PD-1/PD-L1 agents like pembrolizumab and nadofaragene firadenovec have demonstrated efficacy and safety in BCG-unresponsive NMIBC, leading to regulatory approval. Additionally, BCG combined with immunostimulatory protein complexes (e.g., N-803) achieved high complete response rates while preserving quality of life...Promising results have also been observed with intravesical oncolytic immunotherapy combined with systemic anti-PD-1 therapy in cisplatin-ineligible MIBC. These advancements underscore the potential of intravesical and systemic immunotherapies to improve bladder cancer outcomes and warrant further investigation."

Journal • Review • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Nadofaragene firadenovec: “The CHMP was updated on the discussions at the CAT. The committee discussed the issues identified in this application”; Muscle invasive bladder cancer (European Medicines Agency) - CHMP Final Minutes of the meeting on 22 - 25 Apr 2025: “The committee adopted the CHMP recommendation and scientific discussion together with the list of questions as adopted by CAT”

CHMP • Bladder Cancer • Oncology

Safety and Efficacy of FE 999326 Administered Intravesically to Japanese Subjects With High-grade, BCG Unresponsive, Non-muscle Invasive Bladder Cancer (NMIBC) (clinicaltrials.gov) - P3 | N=25 | Active, not recruiting | Sponsor: Ferring Pharmaceuticals | Trial primary completion date: Oct 2025 ➔ Nov 2029

Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

ABLE-41: ADSTILADRIN Early Utilization and Outcomes in the Real World Setting (clinicaltrials.gov) - P=N/A | N=400 | Recruiting | Sponsor: Ferring Pharmaceuticals | Trial completion date: Dec 2025 ➔ Dec 2027 | Trial primary completion date: Dec 2025 ➔ Dec 2027

Real-world evidence • Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Outcomes of Reinduction With Nadofaragene Firadenovec. (PubMed, J Urol) - No abstract available

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

IP02-36 Use of Rectal Diazepam to Prevent Bladder Spasms and Leakage of Medication During Intravesical Administration of Nadofaragene Firadenovec in BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer: Erratum. (PubMed, J Urol) - No abstract available

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Intravesical interferon-α2b gene therapy with nadofaragene firadenovec-vncg: a contemporary review. (PubMed, Future Oncol) - "Today, nadofaragene firadenovec-vncg represents the first-line treatment option for patients with BCG-unresponsive disease as an alternative to cystectomy. Advances in our knowledge of the tumor microenvironment, gene therapy techniques, and tumor biology have contributed to this important discovery, with future studies aimed to optimize the efficacy of this therapy through improved patient selection, disease prognostication, and development of combination strategies."

Journal • Review • Bladder Cancer • Gene Therapies • Genito-urinary Cancer • Oncology • Solid Tumor

ABLE-22: A Trial to Evaluate Intravesical Nadofaragene Firadenovec Alone or in Combination With Chemotherapy or Immunotherapy in Participants With High-grade BCG Unresponsive Non-muscle Invasive Bladder Cancer (clinicaltrials.gov) - P3 | N=250 | Recruiting | Sponsor: Ferring Pharmaceuticals | Trial primary completion date: Dec 2030 ➔ Jun 2028

Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Emerging bladder-sparing treatments for high risk non-muscle invasive bladder cancer. (PubMed, Bladder Cancer) - "Emerging BSTs include immune checkpoint inhibitors like pembrolizumab and novel agents such as nadofaragene firadenovec and nogapendekin alfa inbakicept (IL-15)...Gene therapies and targeted agents like CG0070 and EG-70 are also gaining traction for their innovative mechanisms...Despite advancements, challenges remain in balancing efficacy, safety, and cost-effectiveness within diverse healthcare settings. This narrative review highlights the evolving landscape of BSTs for HR-NMIBC, emphasising the need for robust clinical evidence to refine patient selection and optimise outcomes."

Journal • Review • Bladder Cancer • Gene Therapies • Genito-urinary Cancer • Oncology • Solid Tumor • IL15