On April 30, 2024 Photocure ASA (OSE: PHO), the Bladder Cancer Company, reported its participation in the American Urological Association Annual Congress (AUA 2024) to be held May 3-6, 2024 in San Antonio, TX, USA (Press release, PhotoCure, APR 30, 2024, View Source [SID1234642444]).

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Two AUA program highlights will feature Blue Light Cystoscopy with Cysview study data:

On Sunday, May 5th, Dr. Sanjay Das will present the study, "Use of Blue Light Cystoscopy Among Non-Muscle Invasive Bladder Cancer Patients and Outcomes in an Equal Access setting: A Propensity Scored Matched Analysis"
The study, known as BRAVO (Bladder Cancer Recurrence Analysis in Veterans and Outcomes), is a retrospective, propensity score matched analysis that evaluated oncologic outcomes following BLC compared to WLC alone in patients from the Veterans Affairs (VA) Healthcare System.

(PD48: Bladder Cancer: Non-invasive III,
Sunday, May 5, 2024 1:00 PM to 3:00 PM, room 304A)
Monday, May 6th, Poster presentation by Dr. Hailong Hu: "Blue Light Cystoscopy versus White Light Cystoscopy for the Detection of Bladder Cancer using modern HD 4K equipment: An Analysis of Pivotal Trial and Real-World Data". This pooled meta-analysis includes data from a randomized clinical trial and a supporting real-world evidence study conducted in China.

(MP71: Bladder Cancer: Non-invasive IV,
Monday, May 6, 2024 9:30 AM to 11:30 AM, room 302B)

AUA Congress attendees can meet the Photocure team on booth number 601 and gain hands-on experience in the blue light cystoscopy with Cysview procedure using the Saphira HD equipment.

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About Bladder Cancer

Bladder cancer ranks as the 8th most common cancer worldwide – the 5th most common in men – with 1 949 000 prevalent cases (5-year prevalence rate)1a, 614 000 new cases and more than 220 000 deaths in 2022.1b
Approx. 75% of all bladder cancer cases occur in men.1 It has a high recurrence rate with up to 61% in year one and up to 78% over five years.2 Bladder cancer has the highest lifetime treatment costs per patient of all cancers.3
Bladder cancer is a costly, potentially progressive disease for which patients have to undergo multiple cystoscopies due to the high risk of recurrence. There is an urgent need to improve both the diagnosis and the management of bladder cancer for the benefit of patients and healthcare systems alike.
Bladder cancer is classified into two types, non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), depending on the depth of invasion in the bladder wall. NMIBC remains in the inner layer of cells lining the bladder. These cancers are the most common (75%) of all BC cases and include the subtypes Ta, carcinoma in situ (CIS) and T1 lesions. In MIBC the cancer has grown into deeper layers of the bladder wall. These cancers, including subtypes T2, T3 and T4, are more likely to spread and are harder to treat.4

1 Globocan. a) 5-year prevalence / b) incidence/mortality by population. Available at: View Source, accessed [February 2024].
2 Babjuk M, et al. Eur Urol. 2019; 76(5): 639-657
3 Sievert KD et al. World J Urol 2009;27:295–300
4 Bladder Cancer. American Cancer Society. View Source

About Hexvix/Cysview (hexaminolevulinate HCl)

Hexvix/Cysview is a drug that preferentially accumulates in cancer cells in the bladder, making them glow bright pink during Blue Light Cystoscopy (BLC). BLC with Hexvix/Cysview, compared to standard white light cystoscopy alone, improves the detection of tumors and leads to more complete resection, fewer residual tumors, and better management decisions.
Cysview is the tradename in the U.S. and Canada, Hexvix is the tradename in all other markets. Photocure is commercializing Cysview/Hexvix directly in the U.S. and Europe and has strategic partnerships for the commercialization of Hexvix/Cysview in China, Chile, Australia, New Zealand and Israel. Please refer to View Source for further information on our commercial partners.

On April 30, 2024 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that Roche issued an Investor Update regarding anti-cancer agent/ALK inhibitor Alecensa (alectinib). The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) recommended to approve Alecensa monotherapy as adjuvant treatment following complete tumor resection for adult patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer at high risk of recurrence (Press release, Chugai, APR 30, 2024, View Source;category= [SID1234642443]).
*Stage IB (tumours ≥ 4 cm) – IIIA non-small cell lung cancer (UICC/AJCC 7th edition)

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Please refer to the link below for details of the Investor Update:

CHMP recommends EU approval of Roche’s Alecensa as the first adjuvant treatment for resected ALK-positive early-stage lung cancer
View Source

On April 29, 2024 Bright Biologics reported the company and Asieris Pharmaceutical have signed a collaboration agreement to advance the development of next-generation bispecific and trispecific antibody-drug conjugates (ADCs) (Press release, Bright Biologics, APR 29, 2024, View Source [SID1234656214]). This partnership will combine Asieris’ proprietary linker-payload technology with Bright’s innovative bispecific and trispecific antibodies to create and commercialize novel ADC therapies for cancer treatment.

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On April 29, 2024 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics, reported a comprehensive, peer-reviewed publication of preclinical data supporting MP0533’s proposed unique mechanism of action (MoA) for the treatment of acute myeloid leukemia (AML) in Cancer Immunology Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Molecular Partners, APR 29, 2024, View Source [SID1234655797]). The publication collates and discusses multiple studies undertaken to characterize MP0533’s preclinical profile and evaluate its therapeutic potential.

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Developing safe and efficacious targeted therapies for patients with AML has proven challenging as AML cells share many of the relevant target antigens with healthy cells. Through its unique MoA, MP0533 was designed to simultaneously target the proteins CD33, CD123, and CD70, which are commonly co-expressed on AML cells and rarely on healthy cells. MP0533’s binding strength increases with the number of target proteins present, leading to increased engagement of T cells when at least two of the targets are present. This results in preferential killing of AML cells.

The data published by Bianchi et al in Cancer Immunology Research in collaboration with the University of Bern build on the results presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in December 2021 and 2022, and support MP0533’s intended MoA. MP0533 induces selective T cell-mediated killing of AML cell lines, as well as patient bone marrow-derived AML blasts and leukemic stem cells (LSCs) expressing two or three of the target antigens, while sparing healthy hematopoietic stem cells, blood and endothelial cells. MP0533 also demonstrated reduced risk of T cell fratricide observed with other CD70-targeting agents related to CD70’s upregulation on activated T cells. MP0533 was equivalent to non-CD70 targeting therapies in terms of impact on T cell count and viability, further supporting its potentially favorable on-target, off-tumor profile.

MP0533 led to tumor-localized T-cell activation and efficacious tumor regression in an antigen-dependent manner across different in vivo models. Notably, when compared to other T cell engagers that target single antigens, MP0533 led to lower levels of cytokine release, findings that were confirmed through in vitro, in vivo, and ex vivo studies. This included IL-6, a cytokine known as a primary driver of cytokine release syndrome, a systemic toxicity that has so far limited the development of T cell engagers as potential treatment options of AML. Finally, an evaluation of MP0533 in combination with azacitidine and venetoclax, two chemotherapeutic drugs used in AML, suggest the MoAs may be synergistic in terms of LSC killing.

MP0533 is currently being evaluated in a Phase 1/2a trial in patients with relapsed/refractory AML or myelodysplastic syndrome (MDS/AML), and the Company presented positive initial data from the first four dosing cohorts at the ASH (Free ASH Whitepaper) Annual Meeting and Exposition in December 2023. The trial is currently dosing patients in cohort 7. The Company expects to present an update from the study in H1 2024.

For more information about the publication, visit:

The CD33xCD123xCD70 Multispecific CD3-Engaging DARPin MP0533 Induces Selective T Cell–Mediated Killing of AML Leukemic Stem Cells

Reference:
Bianchi M et al. Cancer Immunol Res 2024. Epub ahead of print April 29, 2024.

About MP0533
MP0533 is a novel tetra-specific T cell-engaging DARPin, which simultaneously targets the antigens CD33, CD123 and CD70 on AML cells as well as the immune activator CD3 on T cells. AML cells commonly co-express at least two of the three target antigens, whereas most healthy cells only have one or none. MP0533 binds with increasing avidity as the number of its target antigens present increases, dramatically favoring binding to AML cells over healthy cells. This unique avidity-driven mode of action is designed to enable T cell-mediated killing of AML cells while preserving a therapeutic window that minimizes damage to healthy cells.

About DARPin Therapeutics
DARPin (Designed Ankyrin Repeat Protein) therapeutics are a new class of custom-built protein drugs based on natural binding proteins that open new dimensions of multi-functionality and multi-target specificity in drug design. The flexible architecture, intrinsic potential for high affinity and specificity, small size and high stability of DARPins offer benefits to drug design over other currently available protein-based therapeutics. DARPin candidates can be radically simple, with a single DARPin unit acting as the delivery vector to a specific target; or multispecific, with the possibility of engaging more than five targets, and combining multiple and conditional functionalities in a unique DARPin drug candidate. The DARPin platform is a rapid and cost-effective drug discovery engine, producing drug candidates with optimized properties and high production yields. DARPin therapeutics have been clinically validated across several therapeutic areas and developed through to the registrational stage.

On April 30, 2024 Genmab A/S (Nasdaq: GMAB) and Pfizer Inc. (NYSE: PFE) reported that the U.S. Food and Drug Administration (FDA) has approved the supplemental Biologics License Application (sBLA) for TIVDAK (tisotumab vedotin-tftv) for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy (Press release, Pfizer, APR 30, 2024, View Source [SID1234643134]). This FDA action converts the September 2021 accelerated approval of TIVDAK to a full approval. TIVDAK is the first antibody-drug conjugate (ADC) with demonstrated overall survival data to be granted full FDA approval in this patient population.

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The approval is based on results from the global, randomized, Phase 3 innovaTV 301 clinical trial (NCT04697628), in which TIVDAK met its primary endpoint of overall survival (OS) in patients with previously treated recurrent or metastatic cervical cancer compared to chemotherapy. Secondary endpoints of progression-free survival (PFS) and a confirmed objective response rate (ORR) were also met. In October 2023, results from the innovaTV 301 study were initially disclosed during the Presidential Symposium at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress.

"As a treating physician, it is encouraging to see overall survival data among these patients and a manageable safety profile with tisotumab vedotin," said Brian Slomovitz, M.D., Director of Gynecologic Oncology and Co-Chair of the Cancer Research Committee at Mount Sinai Medical Center, Miami Beach. "Treatment options for patients with advanced or recurrent cervical cancer are limited. The five-year survival rate for patients who have metastatic disease at diagnosis is less than 20% in the U.S.i There is a high unmet need for more treatment options that have demonstrated survival benefit in the contemporary treatment landscape. The approval of tisotumab vedotin brings us a step closer to fulfilling that need."

The innovaTV 301 study met its primary endpoint of OS, demonstrating a 30% reduction in the risk of death compared with chemotherapy (Hazard ratio [HR]: 0.70 [95% CI: 0.54, 0.89], two-sided p=0.0038ii). Median OS for patients treated with TIVDAK was 11.5 months [95% CI: 9.8-14.9] versus chemotherapy 9.5 months [95% CI: 7.9-10.7]. 

"The full FDA approval of TIVDAK represents a significant achievement for women with recurrent and metastatic cervical cancer, reinforcing TIVDAK as a treatment option that has proven to extend survival in patients whose disease has advanced after initial treatments," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "This milestone underscores the importance of our ongoing clinical development program to assess the full potential of tisotumab vedotin as a treatment option in other indications."

"Recurrent or metastatic cervical cancer is a particularly devastating and mostly incurable disease, and patients are in need of survival-extending treatment options," said Chris Boshoff, M.D., Ph.D., Chief Oncology Officer, Executive Vice President at Pfizer. "Today’s full approval by the FDA reinforces the important role of TIVDAK for these patients, as the first antibody-drug conjugate with statistically significant prolonged overall survival data."

The safety profile of TIVDAK in innovaTV 301 was consistent with its known safety profile as presented in the U.S. prescribing information which includes a BOXED WARNING for Ocular Toxicity. No new safety issues were identified. The most common (≥25%) adverse reactions, including laboratory abnormalities, in patients receiving TIVDAK were hemoglobin decreased (41%), peripheral neuropathy (38%), conjunctival adverse reactions (37%), aspartate aminotransferase increased (34%), nausea (33%), alanine aminotransferase increased (30%), fatigue (28%), sodium decreased (27%), epistaxis (26%), and constipation (25%).

The sBLA application received a Priority Review Designation, which is granted by the U.S. FDA to medicines that may offer significant advances in treatment or may provide a treatment where no adequate therapy exists.iii TIVDAK was granted accelerated approval in the U.S. by the FDA in September 2021, based on tumor response and durability of response from the innovaTV 204 pivotal Phase 2 single-arm clinical trial evaluating TIVDAK as a monotherapy in patients with previously treated recurrent or metastatic cervical cancer.

"Today marks a great day for patients, especially adults battling advanced cervical cancer," said Tamika Felder, cervical cancer patient advocate and Founder and Chief Visionary Officer, Cervivor, Inc. "This full approval opens up new treatment paths for this patient community who have long faced limited options."

About Cervical Cancer
Cervical cancer remains a disease with high unmet need despite advances in effective vaccination and screening practices to prevent and diagnose pre-/early-stage cancers for curative treatment. Recurrent and/or metastatic cervical cancer is a particularly devastating and mostly incurable disease; up to 15% of adults with cervical cancer present with metastatic disease at diagnosisiv,v and, for adults diagnosed at earlier stages who receive treatment, up to 61%vi will experience disease recurrence. It was estimated that in 2023, more than 13,960 new cases of invasive cervical cancer were diagnosed in the U.S. and 4,310 adults would die from the disease.vii

About the innovaTV 301 Trial
The innovaTV 301 trial (NCT04697628) is a global, 1:1 randomized, open-label Phase 3 trial evaluating TIVDAK (tisotumab vedotin-tftv) versus investigator’s choice of single agent chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan or pemetrexed) in 502 patients with recurrent or metastatic cervical cancer who received one or two prior systemic regimens in the recurrent or metastatic setting.

Patients with recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma or adenosquamous histology, and disease progression during or after treatment with chemotherapy doublet +/- bevacizumab and an anti-PD-(L)1 agent (if eligible) are included. The primary endpoint was overall survival. The main secondary outcomes were progression-free survival and objective response rate.

The study was conducted by Seagen, which was acquired by Pfizer in December 2023, in collaboration with Genmab, European Network of Gynaecological Oncological Trial Groups (ENGOT, study number ENGOT cx-12) and the Gynecologic Oncology Group (GOG) Foundation (study number GOG 3057), as well as other global gynecological oncology cooperative groups. For more information about the Phase 3 innovaTV 301 clinical trial and other clinical trials with tisotumab vedotin, please visit www.clinicaltrials.gov.

About TIVDAK (tisotumab vedotin-tftv)
TIVDAK (tisotumab vedotin-tftv) is an antibody-drug conjugate (ADC) composed of Genmab’s human monoclonal antibody directed to tissue factor (TF) and Pfizer’s ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody. Nonclinical data suggest that the anticancer activity of tisotumab vedotin-tftv is due to the binding of the ADC to TF-expressing cancer cells, followed by internalization of the ADC-TF complex and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death. In vitro, tisotumab vedotin-tftv also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.