Vesimune (imiquimod intravesical) / UroGen - LARVOL DELTA

UGN-301 (zalifrelimab), an anti-CTLA4 antibody for use in high-grade non-muscle invasive bladder cancer (GlobeNewswire) - P1 | N=51 | NCT05375903 | Sponsor: UroGen Pharma Ltd. | "Enrollment is complete in the dose escalation phase of UGN-301, alone and in combination with fixed dose UGN-201 or gemcitabine. The treatments demonstrated an acceptable safety profile and were generally well tolerated across dose levels. Responses were observed in both monotherapy and combination therapy arms, and patient follow-up is ongoing to further assess the durability of these responses."

Enrollment closed • P1 data • Bladder Cancer

Programmed Death Ligand 1 Modulation by Bacillus Calmette-Guérin and Toll-Like Receptor Agonists in Distinct Breast Cancer Cell Subtypes. (PubMed, Int J Gen Med) - "MTT (thiazolyl blue tetrazolium bromide) assays were conducted to determine non-cytotoxic concentrations of the immunomodulatory agents: 25 µM IMQ (imiquimod), 10 µg PPG (peptidoglycan), 1 mg LPS (lipopolysaccharide), and two BCG doses (200 µg/mL and 800 µg/mL). These findings suggest distinct immunomodulatory responses between cancer subtypes, emphasizing the need for tailored approaches targeting the PD-1/PD-L1 axis. Further studies should explore the molecular mechanisms underlying these differential effects and assess the potential for combinatorial immunotherapeutic strategies in cancer."

IO biomarker • Journal • Breast Cancer • Immunology • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1

A Window of Opportunity Phase I Study of UGN-201 in Patients With Bladder Cancer Undergoing Radical Cystectomy Protocol #: 2021-0630 (clinicaltrials.gov) - P1 | N=10 | Suspended | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Aug 2025 ➔ Aug 2026 | Trial primary completion date: Aug 2025 ➔ Aug 2026

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

A Phase 1 Dose-escalation Study of UGN-301 in Patients With Recurrent Non-muscle Invasive Bladder Cancer (NMIBC) (clinicaltrials.gov) - P1 | N=51 | Active, not recruiting | Sponsor: UroGen Pharma Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

A PHASE 1 DOSE-ESCALATION STUDY OF UGN-301 (ZALIFRELIMAB) IN PATIENTS WITH RECURRENT NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC) (SUO 2024) - P1 | "The combination arms are investigating UGN-301 with intravesical UGN-201 [imiquimod, a toll-like receptor 7 agonist] (Arm B) or gemcitabine (Arm C). Local delivery of UGN-301 formulated in reverse thermal gel allowed sustained exposure of zalifrelimab in the bladder while limiting systemic exposure and thus mitigating the risk of systemic immune related toxicities associated with CTLA-4 inhibition. At all dose levels, including the MFD, UGN-301 was well tolerated and had a favorable safety profile. Together with the observed efficacy, continued evaluation of UGN-301 for the treatment of NMIBC is warranted."

Clinical • P1 data • Bladder Cancer • Genito-urinary Cancer • Infectious Disease • Nephrology • Oncology • Solid Tumor

A PHASE 1 DOSE-ESCALATION STUDY OF UGN-301 (ZALIFRELIMAB) AS MONOTHERAPY AND IN COMBINATION WITH OTHER AGENTS IN PATIENTS WITH RECURRENT NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC) (SUO 2024) - P1 | "Arm A will investigate UGN-301 monotherapy dose‑escalation, Arm B will investigate UGN-301 dose-escalation + UGN-201 (imiquimod), a toll-like receptor 7 agonist with immune-stimulating anti-tumor effects and Arm C will investigate UGN-301 dose escalation + gemcitabine. Both combinations arms have been initiated and the study is recruiting in the United States, Italy and Spain (NCT05375903). "

Clinical • Combination therapy • Monotherapy • P1 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

The DNA sensor AIM2 mediates psoriasiform inflammation by inducing type 3 immunity. (PubMed, JCI Insight) - "We found elevated levels of mitochondrial DNA in patients with psoriasis, along with high expression of AIM2 in both the human psoriatic epidermis and a mouse model of psoriasis induced by topical imiquimod (IMQ) application. Finally, the genetic absence of inflammasome components downstream AIM2, ASC, and caspase-1 alleviated IMQ-induced skin inflammation. Collectively, our data show that AIM2 is involved in developing psoriasis through its canonical activation."

Journal • Dermatitis • Dermatology • Immunology • Inflammation • Melanoma • Oncology • Psoriasis • Solid Tumor • AIM2 • CASP1 • IL17A • IL23A

A Window of Opportunity Phase I Study of UGN-201 in Patients With Bladder Cancer Undergoing Radical Cystectomy Protocol #: 2021-0630 (clinicaltrials.gov) - P1 | N=10 | Suspended | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Aug 2024 ➔ Aug 2025 | Trial primary completion date: Aug 2024 ➔ Aug 2025

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

A Phase 1 Dose-escalation Study of UGN-301 in Patients With Recurrent Non-muscle Invasive Bladder Cancer (NMIBC) (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: UroGen Pharma Ltd. | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Combination therapy • Monotherapy • Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Urothelial Cancer

A Window of Opportunity Phase I Study of UGN-201 in Patients With Bladder Cancer Undergoing Radical Cystectomy Protocol #: 2021-0630 (clinicaltrials.gov) - P1 | N=10 | Suspended | Sponsor: M.D. Anderson Cancer Center | Recruiting ➔ Suspended

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

Diagnosis and treatment of basal cell carcinoma: European consensus-based interdisciplinary guidelines. (PubMed, Eur J Cancer) - "Topical therapies (5% imiquimod, 5% fluorouracil) and destructive approaches (curettage, electrocautery, cryotherapy, laser ablation) should be considered in patients with low-risk superficial BCC...Hedgehog inhibitors, vismodegib or sonidegib, should be offered to patients with locally advanced and metastatic BCCs...In patients with naevoid basal cell carcinoma syndrome (NBCCS), close surveillance and regular skin examinations are required to diagnose and treat BCCs at early stage. Long-term follow-up is recommended in patients with high-risk BCC subtypes, high-risk sites, multiple BCCs and NBCCS."

Journal • Basal Cell Carcinoma • Oncology

A PHASE 1 DOSE-ESCALATION STUDY OF UGN-301 (ZALIFRELIMAB) AS MONOTHERAPY AND IN COMBINATION WITH OTHER AGENTS IN PATIENTS WITH RECURRENT NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC) (SUO 2022) - P1 | "Arm A will investigate UGN-301 monotherapy dose‑escalation and Arm B will investigate UGN-301 dose-escalation + UGN-201 (imiquimod), a toll-like receptor 7 agonist with immune-stimulating anti-tumor effects. This study is recruiting (NCT05375903). "

Clinical • Combination therapy • Monotherapy • P1 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

A Window of Opportunity Phase I Study of UGN-201 in Patients With Bladder Cancer Undergoing Radical Cystectomy Protocol #: 2021-0630 (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Aug 2022 ➔ Aug 2024 | Trial primary completion date: Aug 2022 ➔ Aug 2024

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

A Phase 1 Dose-escalation Study of UGN-301 in Patients With Recurrent Non-muscle Invasive Bladder Cancer (NMIBC) (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: UroGen Pharma Ltd. | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Monotherapy • Bladder Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Urothelial Cancer

A Phase 1 Dose-escalation Study of UGN-301 in Patients With Recurrent Non-muscle Invasive Bladder Cancer (NMIBC) (clinicaltrials.gov) - P1 | N=60 | Not yet recruiting | Sponsor: UroGen Pharma Ltd.

Combination therapy • Monotherapy • New P1 trial • Bladder Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Urothelial Cancer

A Window of Opportunity Phase I Study of UGN-201 in Patients With Bladder Cancer Undergoing Radical Cystectomy Protocol #: 2021-0630 (clinicaltrials.gov) - P1; N=10; Recruiting; Sponsor: M.D. Anderson Cancer Center; Not yet recruiting ➔ Recruiting

Enrollment open • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

A Window of Opportunity Phase I Study of UGN-201 in Patients With Bladder Cancer Undergoing Radical Cystectomy Protocol #: 2021-0630 (clinicaltrials.gov) - P1; N=10; Not yet recruiting; Sponsor: M.D. Anderson Cancer Center

New P1 trial • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Topical medication as an initial therapeutic option for protruding and non-protruding condylomata acuminata of the distal urethra. (PubMed, BMJ Case Rep) - "Here, we present two cases of low-risk HPV-positive patients with protruding and non-protruding condylomata acuminata of the distal urethra, which were treated successfully by using two different topical regimens (ie, a combination of policresulen and imiquimod for one patient and 5-fluorouracil monotherapy for the other). Although this type of management results in lower rates of tissue destruction and complications and may be given preference as an initial therapeutic option, additional prospective comparative clinical studies are needed to elucidate its potential in similar cases."

Journal • Dermatology • Infectious Disease • Oncology • Urology

[VIRTUAL] Efficacy of imiquimod in the management of lentigo maligna. (ASCO 2020) - P3 | "This randomized prospective study shows that imiquimod reduces the LM area (-50%) after one month of treatment. Reducing the surface of LM with imiquimod is not associated with a higher risk of intralesional excision (marge 5mm), with a significant esthetic result (less excised surface). Research Funding: French Hospital Clinical Research Program in Cancer"

Clinical • Melanoma • Oncology • Solid Tumor • IFNG

UroGen Pharma Reports First Quarter 2021 Financial Results and Recent Corporate Developments (Businesswire) - “Jelmyto® net product revenue of $7.5 million for the first quarter of 2021; The ATLAS trial is expected to enroll approximately 630 patients and is evaluating UGN-102 as a primary non-surgical treatment compared to standard of care – transurethral resection of bladder tumor (TURBT) – in patients diagnosed with LG-IR-NMIBC; Expanded immuno-oncology pipeline with the announcement of two strategic research collaborations during the first quarter of 2021…UroGen and MD Anderson expect to advance the UGN-302 program [UGN-201 (imiquimod) TLR 7/8 + UGN-301 (zalifrelimab) CTLA-4] in the first half of 2021 through nonclinical studies for UGN-301 and UGN-201, as well as a potential human study for UGN-201.”

Clinical • Enrollment status • New trial • Sales • Bladder Cancer • Genito-urinary Cancer • Oncology • Urothelial Cancer

[VIRTUAL] The Role of Interferon Kappa in Psoriasis (ACR-ARHP 2020) - " We used the well-characterized imiquimod (IMQ) psoriasis model for these studies. Overexpression of Ifnk in the epidermis results in increased disease severity after topical application of IMQ, whereas deletion of Ifnk attenuated disease. Although, overexpression of Ifnk alone in the skin does not trigger skin inflammation, our data suggests that epidermal type I IFNs may trigger may act as a rheostat for psoriasis inflammatory responses, driving more inflammatory cells in the skin and promoting a heightened inflammatory and IL-17-oriented response. Together, these data suggest that overproduction of type I IFNs may impact psoriasis development and there may be a role of targeting IFNs in early disease."

Dermatitis • Dermatology • Immunology • Inflammation • Psoriasis • CD8 • IL12A • IL17A • IL1B • IL6 • STAT3 • TNFA

UroGen Pharma Reports Fourth Quarter and Full Year 2020 Financial Results and Recent Corporate Developments (Businesswire) - “UGN-302 [UGN-201 (imiquimod) TLR 7/8 + UGN-301 (zalifrelimab) CTLA-4]: UroGen and MD Anderson expect to progress the UGN-302 program in the first half of 2021, which includes potential non-clinical studies for UGN-301 and UGN-201, as well as potential clinical studies for UGN-201.”

Clinical • Preclinical • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

UroGen Pharma and MD Anderson Announce Strategic Research Collaboration to Advance Investigational Treatment for High-Grade Bladder Cancer (Businesswire) - "UroGen Pharma Ltd...and The University of Texas MD Anderson Cancer Center...announced a strategic three-year collaboration agreement to advance combinatorial intravesical immunotherapy, which is delivered directly into the bladder, for the treatment of high-grade non-muscle invasive bladder cancer (HG-NMIBC). UroGen’s approach involves the local delivery of potent immunomodulators (UGN-201, a TLR 7/8 agonist and UGN-301, an anti-CTLA-4 antibody)....Under the agreement, MD Anderson and UroGen will collaborate on the design and conduct of non-clinical and clinical studies with oversight from a joint steering committee."

Licensing / partnership • Bladder Cancer • Genito-urinary Cancer • Urothelial Cancer

[VIRTUAL] Basal Cell Carcinoma demonstrates a T-cell exclusion immune phenotype in contrast to other anti-PD-1 therapy responsive cutaneous malignancies (SITC 2020) - "Background Basal cell carcinoma (BCC) is considered an immunogenic tumor based on the high tumor mutational burden (TMB), increased incidence in immunocompromised patients, and responsiveness to imiquimod, a toll-like receptor agonist therapy. T-cell exclusion mechanisms mediated through CAFs and desmoplasia, with upregulation of TGF-beta and angiogenic signaling, may play a role. Further investigation into abrogation of these mechanisms is warranted to develop improved anti-PD-1 based therapies for BCC."

IO biomarker • Basal Cell Carcinoma • Melanoma • Oncology • Skin Cancer • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • ARID1A • CAFs • CD8 • CTNNB1 • IFNG • JAK1 • PTCH1 • SMO • TGFB1 • TMB

[VIRTUAL] Basal Cell Carcinoma demonstrates a T-cell exclusion immune phenotype in contrast to other anti-PD-1 therapy responsive cutaneous malignancies (SITC 2020) - "Background Basal cell carcinoma (BCC) is considered an immunogenic tumor based on the high tumor mutational burden (TMB), increased incidence in immunocompromised patients, and responsiveness to imiquimod, a toll-like receptor agonist therapy. T-cell exclusion mechanisms mediated through CAFs and desmoplasia, with upregulation of TGF-beta and angiogenic signaling, may play a role. Further investigation into abrogation of these mechanisms is warranted to develop improved anti-PD-1 based therapies for BCC."

IO biomarker • Basal Cell Carcinoma • Melanoma • Oncology • Skin Cancer • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • ARID1A • CAFs • CD8 • CTNNB1 • IFNG • JAK1 • PTCH1 • SMO • TGFB1 • TMB