On April 8, 2024 Photocure ASA (OSE: PHO), the Bladder Cancer Company, reported its participation in the congress, and two abstract presentations at the 2024 European Association of Urology congress (EAU) in Paris, France, highlighting the benefits of Blue Light Cystoscopy (BLC) in Bladder Cancer management (Press release, PhotoCure, APR 8, 2024, View Source [SID1234641906]).

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The EAU annual meeting is one of the largest international meetings in the urology calendar, showcasing the latest and most relevant clinical and scientific advancements in this area of patient care. This year’s event was held on April 5-8, 2024, and attracted urologists from all over the world. Similar to last year, Photocure will make 2024 EAU bladder cancer session highlights available to healthcare professionals post event, by means of video interviews with the presenters of these sessions on the Photocure booth D26. This highly engaging and successful initiative is once again supported by two of the leading names in Bladder Cancer in Europe, Prof. M. Rouprêt, APHP, Sorbonne University Paris, France and Prof. P. Gontero, Division of Urology, University of Studies of Torino, Italy.

In addition to this educational activity, the EAU scientific program prominently features Photocure’s Hexvix product and/or the blue light cystoscopy procedure in which it is used. In particular, two notable abstract presentations were:

Outpatient laser coagulation of low-grade intermediate risk bladder tumor compared with TUR-BT, 12 months and long-term follow-up of a non-inferiority RCT (Abstract session 36 NMIBC: Benefits and harms of various treatment options, Sunday, 7 April, 17:15-18:45)

Treatment of recurrent low grade intermediate risk bladder tumor is burdensome for patients and health care system. The primary objective of this study was to evaluate 12 months recurrence-free survival after out-patient department photo coagulation of bladder tumors (PC-BT) is non-inferior to PDD-assisted TUR-BT in patients with recurrent Ta low grade bladder tumor. 154 patients were randomized for PC-BT and 146 for TUR-BT. 12 months follow-up data were available for 299 patients. 12 months recurrence-free survival was 42.2% after PC-BT and 44.1% after TUR-BT, the difference 1.9% (95%CI -9.3 to 13.2) in favor of TUR-BT. Regarding 12 months recurrence-free survival, the noninferiority criterion was met. Recurrence-free survival after OPD PC-BT is noninferior to TUR-BT at 12 months follow-up. Incidence of long-term stage progression after PC-BT is noninferior to TUR-BT and very low after both treatment modalities. Treatment of recurrent Ta low grade intermediate risk bladder tumors in out-patient department with PC-BT appears to be a safe alternative to TUR-BT.

Read the abstract: View Source

A prospective, comparative, within-patient controlled multicenter phase III study comparing blue light cystoscopy versus white light cystoscopy for the detection of bladder cancer using modern HD 4K equipment (Abstract session 46, Monday, 8 April, 12:30-14:00)

The study enrolled a total of 158 patients in a randomized controlled trial, and 114 patients underwent Hexvix blue light cystoscopy (BLC) and were in the full analysis set. Among patients diagnosed with Ta, T1, or CIS, 42 out of 97 patients (43.3%) had at least one lesion detected by BLC but not by white light cystoscopy (WLC) (p<0.0001). Thirteen patients had CIS of which 11 (84.6%) showed additional CIS lesions. The BLC detection rates for PUNLMP, CIS, Ta, T1, and T2 ~ T4 tumors were NA, 94.7%, 100%, 98.2%, and 100%, respectively, while the WLC detection rates were NA, 42.1%, 76.1%, 91.2%, and 100%. This study confirms the superiority of HAL BLC over WLC in the detection of bladder cancer even if improved WLC using HD 4K equipment is utilized. In particular, additional high-risk difficult to see CIS lesions have been identified in 85% of all CIS patients only by HAL BLC. The quality of resection is still a key cornerstone in the treatment of NMIBC of which BLC remains a crucial part despite the further development of WLC imaging.

Read the abstract: View Source

"With the rapid advancement of technologies, emerging trends towards precision medicine and introduction of novel targeted agents which are transforming bladder cancer care, there is a renewed emphasis on the importance of the diagnostic process. Getting a correct and timely diagnosis is more important than ever. It’s key to optimizing the subsequent care pathways and treatment decisions," said Anders Neijber, Chief Medical Officer of Photocure. "These new results presented at EAU continue to emphasize the importance of using Blue Light Cystoscopy in the diagnosis of bladder cancer. BLC has been shown to clinically increase TURBT quality, more accurately stage disease, and enable better recurrence monitoring, supporting the long-term utility to help improve the lives of patients with bladder cancer."

"Every year we see new data added to the body of evidence on Hexvix/blue light cystoscopy benefits, including with high-definition equipment. In Europe, our teams focus on helping their customers achieve the best possible image quality for BLC. We are convinced that when it comes to bladder tumor detection methods "seeing is believing", which is also our booth theme for this year’s EAU. Many urologists try BLC, see what they see, and never look back", added Susanne Strauss, Vice President and General Manager Europe.

*TUR-BT/TURBT: trans-urethral resection of bladder tumors

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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 8, 2024 Verismo Therapeutics, a clinical-stage CAR T company developing the novel KIR-CAR platform technology, reported that an abstract has been accepted for poster presentation at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 (AACR 2024), to be held in San Diego on April 5-10, 2024 (Press release, Verismo Therapeutics, APR 8, 2024, View Source [SID1234641905]).

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Presentation Details

Title: Evaluating the relationship of affinity, functional avidity, and in vivo potency in KIR-CAR T cells
Abstract Number: 6332
Date and Time: Tuesday, April 9th: 1:30 – 5:00 p.m.
Presenting Author: Jun Xu, PhD
Description: We have previously shown that a novel killer immunoglobulin receptor (KIR)-based CAR expressed in T cells as a multichain receptor with DAP12 (KIR-CAR T) has enhanced anti-tumor activity compared to conventional second-generation CAR T cells in several preclinical solid tumor models suggesting that this platform may show better activity in aggressive lymphoma. In this study, we aimed to evaluate the relationship of affinity, functional avidity, and in vivo potency of novel CD19 binders in a KIR-based CAR T cell. This study paves the way for developing an improved CD19-specific KIR-CAR T cell therapy for treating pts with B-cell malignancies.

About the KIR-CAR Platform
The KIR-CAR platform is a multi-chain CAR T cell therapy and has been shown in preclinical animal models to be capable of maintaining antitumor T cell activity even in challenging tumor microenvironments. Using NK cell derived KIR and DAP12 split signaling provides a novel combined activation and co-stimulation separate from the usual T cell stimulation pathways. It also enables sustained chimeric receptor expression and improves KIR-CAR T cell long term function. This results in prolonged T cell functional persistence and leads to regression of solid tumors in preclinical models that are resistant to traditional CAR T cell therapies. The KIR-CAR platform is being investigated in combination with many additional emerging technologies to potentially provide the next-generation multimodal targeted immunotherapy for patients in need.

On April 8, 2024 Sapience Therapeutics, Inc., a clinical-stage biotechnology company focused on the discovery and development of peptide therapeutics to address oncogenic and immune dysregulation that drive cancer, reported the presentation of new data on its clinical and pipeline programs during three poster presentations at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place April 5-10, 2024, in San Diego, CA (Press release, Sapience Therapeutics, APR 8, 2024, View Source [SID1234641904]).

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"At AACR (Free AACR Whitepaper) 2024, we are thrilled to present foundational data that support our growing clinical and preclinical pipeline of peptide therapeutics against difficult-to-drug targets, such as β-catenin, C/EBPβ, and c-Jun (AP-1 complex)," said Jim Rotolo, Ph.D., SVP, Research and Translational Sciences. "These data demonstrate the ability of our lead SPEARs, ST316 and ST101, to positively impact the tumor immune microenvironment, providing further evidence of their therapeutic promise. We look forward to ST316 and ST101 continuing to advance through clinical development and moving our AP-1 program into IND-enabling studies."

Sapience scientists will present non-clinical immune-oncology results from both of its clinical programs, ST316, a first-in-class antagonist of β-catenin, and ST101, a first-in-class antagonist of C/EBPβ. Sapience will also present its first disclosure of pre-clinical data describing JunAP, its first-in-class AP-1 complex antagonist targeting the interaction of c-Jun with Fra1.

Poster presentation details and abstract highlights include:

Title: "ST316, a clinical peptide antagonist of beta-catenin, induces anti-tumor immune responses by multiple mechanisms of action"
Session Title: Inflammation in Tumor Initiation and Progression
Location: Poster Section 4
Abstract Number: 5332
Date and Time: Tuesday, April 9, 2024, 1:30 PM to 5:00 PM

ST316 is a first-in-class peptide antagonist of the interaction between β-catenin and its co-activator, BCL9, a complex that drives oncogenic gene expression in multiple cancers where aberrant Wnt/β-catenin pathway signaling is observed, and impacts the tumor immune microenvironment by promoting immunosuppressive myeloid-derived suppressor cell (MDSC) and tumor associated macrophage (TAM) populations. ST316 is currently being evaluated in a Phase 1-2 study (NCT05848739) enrolling patients with selected advanced solid tumors likely to harbor abnormalities of the Wnt/β-catenin signaling pathway.

In nonclinical studies, Sapience evaluated the ability of ST316 to enhance anti-tumor immune responses in combination with anti-PD-1 and anti-TIGIT therapies.
ST316 increases the ratio of proinflammatory M1 macrophages to immunosuppressive M2 macrophages, decreases PD-L1 expression on M2 macrophages and decreases PD1 expression on CD8+ T cells.
ST316 promotes cell surface expression of CD155/PVR to activate T cells in the presence of anti-TIGIT antibody.
In nonclinical in vivo studies, ST316 in combination with anti-PD-1 treatment displays significant anti-tumor activity with accompanied reduction in M2 macrophages.
These data support a paradigm in which ST316 promotes a shift to an immune-active tumor microenvironment via multiple mechanisms, including driving macrophage polarization toward an M1 immune-promoting phenotype, augmenting activity of cytotoxic T cells, and increasing expression of the checkpoint activator CD155/PVR on cancer cells.
Title: "ST101, a clinical C/EBPβ-antagonist peptide, promotes an immune-active tumor microenvironment by multiple cellular mechanisms"
Session Title: The Tumor Microenvironment as a Drug Target
Location: Poster Section 13
Abstract Number: 2909
Date and Time: Monday, April 8, 2024, 1:30 PM to 5:00 PM

ST101 is a peptide antagonist of C/EBPβ that is being evaluated in a Phase 2 clinical study in patients with recurrent and newly diagnosed glioblastoma (NCT04478279).

Sapience evaluated the effect of ST101 on immunosuppressive cell populations and on activation of cytotoxic T cells in macrophage co-culture systems.
ST101 inhibits the immunosuppressive M2 macrophage program, resulting in polarization of macrophages to the proinflammatory M1 phenotype and increasing cytotoxic T cell activation.
In animal models, ST101 enhances the activity of anti-PD-1 treatment by increasing the M1/M2 ratio in the TAM population.
Gene expression analysis of clinical biopsies indicates that ST101 modulates the tumor immune microenvironment by suppressing genes required for M2 macrophage polarization, resulting in an enhanced CD8/Treg ratio.
ST101 represents a novel approach to enhance anti-tumor immune activity and these data suggest its utility for combination strategies in cancers with poor response to immune checkpoint inhibition.
Title: "JunAP, a peptide antagonist against the activator protein 1 transcription factor complex, demonstrates cancer cell cytotoxicity, reduced invasion in vitro and tumor regression in vivo in TNBC models"
Session Title: Oncogenic Transcription Factors
Location: Poster Section 18
Abstract Number: 3051
Date and Time: Monday, April 8, 2024, 1:30 PM to 5:00 PM

AP-1 complexes have been identified as novel therapeutic targets in cancer due to their role in tumor growth, invasion, metastasis, angiogenesis and chemoresistance.
AP-1 complexes consisting of c-Jun and Fra1 are implicated in the survival of a diverse set of tumors.
JunAP targets and blocks c-Jun and Fra1 dimerization, inhibits AP-1 transcriptional activity and inhibits AP-1-dependent cell survival and invasion in vitro.
JunAP demonstrates potent anti-tumor activity in vivo in mouse triple negative breast cancer and melanoma tumor models.
More information can be found on the 2024 AACR (Free AACR Whitepaper) website.

About ST316

ST316 is a first-in-class peptide antagonist of the interaction between β-catenin and its co-activator, BCL9, a complex that drives oncogene expression in multiple cancers where aberrant Wnt/β-catenin pathway signaling is observed. ST316-101 (NCT05848739) is a first-in-human, open-label, Phase 1-2 dose-escalation and expansion study designed to determine the safety, tolerability, PK, PD and early efficacy of ST316. The Phase 1 dose-escalation portion of the Phase 1-2 study is enrolling and dosing patients with select advanced solid tumors that are known to harbor abnormalities of the Wnt/β-catenin signaling pathway. The Company expects to complete the Phase 1 portion of the study in the first half of 2024. Following completion of the study’s Phase 1 portion, the recommended dose will advance to the Phase 2 dose expansion portion of the study in colorectal cancer patients.

About ST101

ST101, a first-in-class antagonist of C/EBPβ, is currently being evaluated in the Phase 2 portion of an ongoing Phase 1-2 clinical study in patients with recurrent GBM (rGBM) (NCT04478279). In an ongoing window-of-opportunity sub-study, ST101 is being evaluated as a monotherapy in rGBM and in combination with radiation and temozolomide in newly diagnosed GBM, with patients receiving ST101 before and after surgical resection. ST101 has been granted Fast Track designation for rGBM from the U.S. FDA and orphan designations for glioma from the U.S. FDA and the European Commission.

On April 8, 2024 Hinge Bio, Inc., a privately-held biotechnology company, reported that Daniel Capon, Ph.D., Chief Scientific Officer, and Juha Punnonen, M.D., Ph.D., Chief Development Officer, are presenting data from the company’s GEM-DIMER program targeting B cell depletion at this year’s American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 in San Diego (Press release, Hinge Bio, APR 8, 2024, View Source [SID1234641903]).

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"Hinge Bio is addressing areas of significant unmet medical need with its revolutionary GEM-DIMER platform, which uses topological engineering to combine the most desirable properties of multiple clinically relevant antibodies into a single molecule with dramatically improved activity, while retaining the robust stability and manufacturability of conventional antibodies," said Dr. Capon. Dr. Punnonen added, "This encouraging preclinical data supports advancing its GEM-DIMER candidate targeting CD19, CD20, and Fc gamma receptors as quickly as possible to clinical investigation in order to treat the large number of patients with B cell mediated diseases who remain resistant to currently approved treatments."

Oral Poster details are as follows:

Beyond antibodies and CAR-T: Topologically-engineered, super-dimeric antibody-like molecules with dual Fc domains for trispecific, bivalent targeting of CD19, CD20, and Fc gamma receptors

Abstract #2730, Session PO.IM01.06 – Single Target and Bispecific Antibodies

Session Date/Time: April 8, 2024, 1:30 PM – 5:00 PM, Section 6

Presenting Authors: Daniel Capon, PhD, Chief Scientific Officer;
Juha Punnonen, MD, PhD, Chief Development Officer

Summary: Hinge Bio’s CD19/CD20-targeting GEM-DIMER molecules are promising candidates to provide efficient depletion of both CD19+ and CD20+ cells, providing potential for broad and deep depletion of B cells with reduced risk of emergence of antigen escape variants. These data support the advancement of these CD19/CD20-targeting GEM-DIMER molecules in multiple indications where depletion of CD19+ and/or CD20+ B cells is needed. Preparations for clinical investigation are ongoing.

On April 8, 2024 Adela, Inc., an innovator in blood testing for minimal residual disease monitoring and early cancer detection through a proprietary genome-wide methylome enrichment technology, reported initial results demonstrating the ability of its MRD assay to predict recurrence in head & neck cancer, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting from April 5-10, 2024 (Press release, Adela, APR 8, 2024, View Source;neck-cancer-at-the-american-association-for-cancer-research-annual-meeting-2024-302109070.html [SID1234641902]).

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"In patients with head & neck cancer, determining the most appropriate course of action following curative intent treatment can be challenging due to the need to balance the potential side effects of treatment with the ramifications of recurrence. Furthermore, detection of recurrence is complicated by inaccuracies of medical imaging and a lack of standardized surveillance procedures", said Scott Bratman MD, PhD, Chief Innovation Officer, Adela and Radiation Oncologist and Clinician-Scientist at Princess Margaret Cancer Centre, University Health Network. "We are highly encouraged by these initial results and the potential for a novel approach to improve care of patients with head & neck cancer."

The ability of Adela’s assay to quantify cfDNA cancer signal and predict recurrence was evaluated in individuals diagnosed with stage I-IVB human papillomavirus (HPV)-negative and HPV-positive head and neck cancer treated at Princess Margaret Cancer Centre, University Health Network. This training analysis included 249 plasma samples collected from 75 patients (a subset of the full cohort of >1,100 plasma samples from >300 individuals). Blood draws occurred before and after curative intent treatment, and in a subset of patients, at 12 and 24 months post-curative intent treatment. Adela’s MRD assay demonstrated the ability to identify patients more likely to recur than not, based on the blood draw following curative intent treatment (i.e., landmark), and also at the longitudinal timepoints. Significant differences in recurrence-free survival (RFS) were observed, with a hazard ratio (HR) of 10.97 (P<0.001) at the landmark timepoint, and an HR of 22.83 (P<0.001) longitudinally, when patients were stratified by MRD positivity.

"By identifying patients with head & neck cancer who are more likely to recur, our MRD test has the potential to provide clinicians with useful information that may aid in their decisions regarding the use of adjuvant therapy as well as enable recurrences to be detected and treated earlier," said Dr. Anne-Renee Hartman, Chief Medical Officer of Adela. "These initial results give us confidence that our tissue-agnostic approach to MRD detection for both HPV-positive and HPV-negative head & neck cancer can address the strong unmet need in this particular indication."

Validation results from a held-out test set from the cohort will be presented at a future meeting. Adela plans to commercialize its tissue agnostic test for minimal residual disease (MRD) monitoring in 2025.

Data will also be presented at AACR (Free AACR Whitepaper) on the analytical performance of Adela’s genome-wide methylome enrichment platform on April 9, 2024.

Presentation Details

Abstract # 2427: The development of a tissue-agnostic genome-wide methylome enrichment MRD assay for applications across the cancer care continuum for head and neck malignancies
Geoffrey Liu1
Mon Apr 8, 2024 9 am-12:30 pm PT
Section 40 Poster Board Number 23

Abstract # 5024: Analytical performance of a genome-wide methylome enrichment platform to detect minimal residual disease from plasma-derived cell-free DNA
Hestia Mellert2
Tues Apr 9, 2024 9am – 12:30pm PT
Section 40 Poster Board Number 11