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

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

Global insights into the management of BCG-unresponsive non-muscle invasive bladder cancer: a narrative review of provider surveys. (PubMed, Transl Androl Urol) - "Preferences for intravesical chemotherapy agents differed by region: gemcitabine (Gem) was commonly used in the US and Arab countries; epirubicin and doxorubicin were favored in China; mitomycin C (MMC) was preferred in Europe. While most urologists were familiar with gemcitabine/docetaxel (Gem/Doce), its actual use in clinical practice remained limited...Notably, at the time of the surveys, newly Food and Drug Administration (FDA)-approved therapies like nadofaragene and pembrolizumab were rarely used. Global practice patterns for BCG-unresponsive disease vary widely across regions, highlighting the need for a more unified, consensus-driven approach to the use of evolving bladder-sparing therapies and clinical guidelines."

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

TR-002 for the Treatment of Advanced, Unresectable or Metastatic Solid Tumors and Unresectable or Metastatic, Refractory Pancreatic Adenocarcinoma (clinicaltrials.gov) - P1 | N=52 | Recruiting | Sponsor: University of California, Davis | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2030 ➔ Feb 2030

Enrollment open • Trial completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Cost per Responder of TAR-200 vs. Other FDA-Approved Novel and Generic Treatments Among Bacillus Calmette-Guérin-Unresponsive High-Risk Non-Muscle Invasive Bladder Cancer With Carcinoma in Situ in the United States (ISPOR-EU 2025) - "Patients treated with TAR-200 monotherapy were compared to those treated with pembrolizumab, nadofaragene firadenovec (NF), nogapendekin alfa inbakicept (NAI)+BCG (with and without reinduction), or valrubicin based on published clinical trial data. TAR-200 demonstrated the highest proportion of patients achieving and sustaining CR for ≥12 months, translating to substantial cost savings per responder compared to other FDA-approved treatments for BCG-UR HR-NMIBC with CIS."

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

Gene Therapy for BCG-Unresponsive Non-Muscle Invasive Bladder Cancer: Current Evidence and Future Directions. (PubMed, Cancers (Basel)) - P1/2, P2, P3 | " Nadofaragene firadenovec, a recombinant adenovirus delivering interferon alpha-2b (IFNα2b), is the first FDA-approved gene therapy for BCG-unresponsive NMIBC with carcinoma in situ (CIS)...Cretostimogene grenadenorepvec (CG0070), an oncolytic vector, demonstrated a 47% 6-month CR rate in a phase II study (NCT02365818). Detalimogene voraplasmid (EG-70), a nonviral gene therapy, demonstrated a 47% 6-month CR in a phase I/II study (NCT04752722). Future advances are likely to focus on patient selection, novel vectors, and combination strategies to improve treatment outcomes. Gene therapy represents a significant addition to the bladder cancer treatment landscape by offering bladder-sparing alternatives where conventional therapies are limited."

Journal • Review • Bladder Cancer • Gene Therapies • Genito-urinary Cancer • Oncology • Solid Tumor • Urethral Cancer • Urothelial Cancer • IFNA1

Real-world outcomes of nadofaragene firadenovec for BCG-unresponsive non-muscle-invasive bladder cancer: A multicenter experience. (PubMed, Urol Oncol) - "Real-world data confirm the efficacy and safety of nadofaragene firadenovec, clarifying its role in the management of BCG-unresponsive NMIBC."

Journal • Real-world evidence • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Pharmacotherapy for bladder spasm and irritative lower urinary tract symptoms associated with intravesical therapy for bladder cancer: a review of available evidence. (PubMed, Transl Androl Urol) - "This concern is of particular relevance given the recent approval of several novel intravesical agents for the treatment of Bacillus Calmette-Guérin (BCG)-unresponsive NMIBC, including nadofaragene firadenovec and nogapendekin alfa inbakicept. In this review, we evaluate the etiology of bladder spasms and irritative LUTS associated with currently approved intravesical therapies for bladder cancer and current approaches to preventing and managing them. By synthesizing available evidence and clinical practice insights, we aim to provide practical recommendations to optimize intravesical therapy for bladder cancer outcomes."

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

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

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