On October 13, 2023 InterVenn Biosciences, a life sciences company pioneering glycoproteomics, reported the publication of their discovery work in Advanced Adenoma (AA) and Colorectal Cancer (CRC) early disease detection in the flagship journal of the American Gastroenterological Association, Gastroenterology (Press release, InterVenn Biosciences, OCT 13, 2023, View Source [SID1234635962]). This groundbreaking research in early detection of CRC represents an advancement in early diagnosis through serum glycoproteome profiling. InterVenn’s GlycoVision platform leverages advanced liquid chromatography-mass spectrometry (LC-MS) combined with artificial intelligence (AI) and neural networks (NN) to interrogate a new layer of biology, enabling novel insights and discoveries.

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The results published in Gastroenterology establish the groundwork for a blood-based CRC screening modality using artificial intelligence to reveal the earliest stages of colorectal cancer. The proprietary LC-MS and AI/NN platform, GlycoVision, has been developed to accelerate data analysis of biological information that has not previously been practical or efficient.

The research involved a comprehensive case-control analysis using well-annotated blood samples from 279 cases (CRC and advanced adenomas) and 296 control samples. InterVenn’s sophisticated LC-MS-based glycoproteomic quantification workflow was employed, resulting in the development of a novel multivariable classifier model using six key biomarkers, which, when applied to a test set, achieved an Area under the Receiver Operating Characteristic curve (AuROC) of 0.96, signifying notable sensitivity and specificity in detecting both CRC and advanced adenoma. The classifier exhibited a sensitivity of 90.9% for advanced adenoma without high grade dysplasia, 85.7% for Advanced Adenoma with High Grade Dysplasia and 89.8% for all stages of CRC, including 91.2% for early-stage (stage 1 and 2) CRC, and 89.4% for late-stage (stage 3 and 4) CRC, along with high specificity of 89% for normal findings.

"InterVenn’s novel AI-powered glycoprotein-based strategy is among the most differentiated and compelling value propositions in the diagnostic industry," said Josh Stahl, InterVenn’s recently appointed CEO. "The resulting performance of the GlycoVision platform has the potential to aid patients, providers, and payers in the early diagnosis of colorectal cancer."

"This collaborative study, conducted in partnership with some of the world’s foremost experts in colorectal cancer, represents a pivotal milestone in advancing the development of an innovative blood-based CRC screening test," stated Daniel Hommes, gastroenterologist and Chief Medical Officer.

Details on the Publication:

Desai K, Gupta S, May FP, Xu G, Shaukat A, Hommes DW, NICE-AA/CRC- Consortium, Early detection of advanced adenomas and colorectal carcinoma by serum glycoproteome profiling., Gastroenterology (2023), doi: View Source

On October 13, 2023 SOTIO Biotech, a clinical-stage immuno-oncology company owned by PPF Group, reported that it will discontinue the currently ongoing clinical trials of nanrilkefusp alfa as monotherapy and in combinations with pembrolizumab and cetuximab (Press release, SOTIO, OCT 13, 2023, View Source [SID1234635961]). Interim data from SOTIO’s clinical trials of nanrilkefusp alfa have shown insufficient efficacy to warrant further development in larger randomized trials in these specific indications and combinations. Interim data revealed no major safety issues in any of the trials. SOTIO is exploring options for alternative clinical development paths for nanrilkefusp alfa, including in combination with cell therapies, which has already generated promising preclinical data.

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Based upon the interim data, effective immediately, enrollment in the AURELIO-03, AURELIO-04, and AURELIO-05 clinical trials will be stopped. SOTIO will continue to fulfill its obligations to patients currently enrolled in these trials, who will be able to continue treatment under the current protocol at the discretion of their principal investigator.

"While we are disappointed with this outcome, we will continue to gather and analyze the full body of data from these studies to inform our future development plans for nanrilkefusp alfa, especially its potential utility in combination with other cancer immunotherapies," said Richard Sachse, M.D., Ph.D., chief medical officer of SOTIO. "We are grateful to the patients, families and investigators that participated in these trials and whose contributions are essential to improving the standard of care for solid tumor cancers."

SOTIO will continue to advance its immunocytokine platform including preclinical development of SOT201, a next-generation PD-1-inhibiting cytokine that is on track to enter Phase 1 clinical development in the second quarter of next year. SOTIO will also continue to explore nanrilkefusp alfa with partners who are developing treatment modalities with a synergizing mode of action.

"SOTIO remains committed to developing immuno-oncology therapies that can improve outcomes for patients with solid tumors. With SOT201 we are advancing an even more differentiated program toward the clinic, combining checkpoint inhibition with IL-15 activation to produce a dual-acting therapy of great potential," said Radek Spisek, M.D., Ph.D., chief executive officer of SOTIO. "We will continue to actively advance current and additional programs across our three platforms, and as such we believe SOTIO to be well-positioned for success with our diversified pipeline of next-generation immunotherapies."

On October 13, 2023 Boundless Bio, a clinical stage, next-generation precision oncology company interrogating extrachromosomal DNA (ecDNA) biology to deliver transformative therapies to patients with previously intractable oncogene amplified cancers, reported that it will present preclinical data on its second ecDNA-directed therapy (ecDTx), BBI-825, as well as present additional research on the intrinsic genomic plasticity of cancer cells enabled by ecDNA at the 2023 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) (Press release, Boundless Bio, OCT 13, 2023, View Source [SID1234635960]).

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BBI-825 is a novel, orally available, selective inhibitor of ribonucleotide reductase (RNR), which is a rate-limiting enzyme in the cellular production of deoxynucleotide triphosphates (dNTPs), essential building blocks for ecDNA assembly and repair in cancer cells. BBI-825 has demonstrated RNR inhibition in a host of tumor cell lines and tumor regressions in ecDNA-enabled preclinical cancer models and is currently being evaluated in Investigational New Drug (IND)-enabling studies. BBI-825 was discovered using Boundless Bio’s proprietary Spyglass platform, a drug discovery engine to identify and preclinically validate targets that are essential for cancer cells’ reliance on ecDNA for growth, treatment resistance, and survival.

"We are excited to unveil our second ecDTx program, BBI-825, which has demonstrated promising preclinical proof of concept in multiple tumor types and across different oncogene amplifications, particularly in resistance associated with targeted therapy treatment of MAPK pathway activated cancers," said Chris Hassig, Ph.D., Chief Scientific Officer of Boundless Bio. "In addition to single agent anti-tumor activity, BBI-825 also has shown synergistic activity when combined with specific targeted therapies in ecDNA-enabled in vivo tumor models, and in particular, cancer models that develop resistance amplifications on ecDNA in response to KRASG12C inhibitors in KRASG12C mutated CRC. We believe a selective, oral RNR inhibitor has broad potential for patients with ecDNA-enabled and oncogene amplified cancers and that the discovery and preclinical validation of BBI-825 underscores the power of our Spyglass platform."

The second poster presentation extends the field’s understanding of ecDNA and its key role in enabling resistance to cancer therapy. Unique properties of ecDNA drive genomic plasticity and tumor heterogeneity, enabling rapid acquired resistance to targeted therapies and resulting in poor patient outcomes; however, the potential adaptive and resistance properties in the chromosomal state are not well characterized. The findings from this study provide a model for how cancer cells with ecDNA-derived, chromosomally reintegrated homogeneous staining regions (HSR) retain the capacity to amplify ecDNA, thus further enabling rapid adaptation to therapeutic pressure and highlighting the urgent need for ecDNA-directed therapies for patients with oncogene amplified cancers.

Details of today’s presentations are as follows:

Title: A novel, potent and selective ribonucleotide reductase (RNR) inhibitor, BBI-825, blocks extrachromosomal DNA (ecDNA) amplification-mediated resistance to KRASG12C inhibitor in colorectal cancer (CRC)
Abstract Number: B082
Session: Poster Session B
Date/Time: Friday, October 13 | 12:30 – 4:00 pm ET

Title: Intrinsic genomic plasticity of extrachromosomal DNA (ecDNA) enables oncogene amplified tumor cells to develop rapid acquired resistance to targeted therapy
Abstract Number: B092
Session: Poster Session B
Date/Time: Friday, October 13 | 12:30 – 4:00 pm ET

About BBI-825

BBI-825 is a novel, orally available, selective inhibitor of ribonucleotide reductase (RNR), a rate-limiting enzyme responsible for cellular production of deoxyribonucleotide triphosphates (dNTPs), the building blocks of DNA, and essential to the assembly and repair of ecDNA. In preclinical studies, BBI-825 starved ecDNA-reliant cancer cells of dNTPs, depleted ecDNA, and was synthetic lethal in ecDNA-bearing cancer cells. BBI-825 has demonstrated preclinical in vivo proof of concept in multiple tumor types and across different oncogene amplifications, including both driver oncogene and resistance settings, particularly in MAPK pathway activated cancers. RNR was identified and preclinically validated as an ecDNA essential target via Boundless Bio’s proprietary Spyglass platform and led to the development of BBI-825, which is currently being evaluated in IND-enabling studies.

On October 13, 2023 Geneseeq Technology Inc. reported that Geneseeq’s Non-Small Cell Lung Cancer Tumor Mutational Burden Test Kit (Reversible terminator sequencing method) (NSCLC TMB Kit) has gained approval from the Chinese National Medical Products Administration (NMPA) on October 12, 2023 as a Breakthrough Medical Device (Press release, Geneseeq, OCT 13, 2023, View Source [SID1234635959]).

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This NSCLC TMB kit entered the NMPA special examination and approval procedures for Breakthrough Medical Devices in January 2020. With the NMPA approval, this kit is used for in vitro qualitative detection of TMB in FFPE tissue samples from patients with EGFR/ALK-negative non-squamous NSCLC. This is the first next-generation sequencing (NGS)-based TMB test kit approved in China with a large gene panel covering 425 cancer-associated genes (GENESEEQPRIME). TMB is a predictive biomarker for the efficacy of immune checkpoint inhibitor therapy.

Prior to this, Geneseeq already had one NGS-based CDx kit for NSCLC, ESSENCARE (EGFR/ALK/ROS1/BRAF/KRAS/HER2 mutation testing kit), approved by the NMPA through the Breakthrough Medical Devices pathway. GENESEEQPRIME was also CE-IVD marked by the European Medicines Agency in August 2023 for detecting single nucleotide variants, gene amplifications/deletions, translocations, TMB, and microsatellite instability in patients with solid tumors.

"This approval will significantly benefit the clinical implementation of immunotherapy in China with a standardized TMB assessment assay," Dr. Yang Shao, founder and CEO of Geneseeq Group, said in a statement.

On October 13, 2023 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 two posters at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), taking place October 11-15, 2023, in Boston, MA (Press release, Sapience Therapeutics, OCT 13, 2023, View Source [SID1234635958]).

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Poster Presentation Details:

Title: "Clinical and Biological Activity of ST101, a Peptide Antagonist of C/EBPβ, in Recurrent Glioblastoma (rGBM) Patients. Results From the rGBM Cohort of a Multi-Cohort Phase 2 Study"
Poster Number: B038
Session Title: Poster Session B
Date/Time: Friday, October 13, 2023, 12:30 pm-4:00 pm
Session location: Level 2, Exhibit Hall D

ST101 is a first-in-class antagonist of C/EBPβ that has demonstrated clinical proof-of-concept in advanced solid tumors. ST101 is currently being evaluated in the Phase 2 portion of an ongoing Phase 1-2 clinical study in patients with advanced unresectable and metastatic solid tumors (NCT04478279).
The poster summarized clinical data from ST101’s recurrent Glioblastoma (rGBM) Phase 2 expansion cohort of 30 patients. The GBM cohort showed ≥ 1 response in the first 15 patients, triggering the criteria to expand to a total of 33 patients enrolled; 30 were evaluable for efficacy in this cohort.
Key Conclusions:
ST101 demonstrates the ability to pass through the blood-brain-barrier and engage C/EBPβ.
Single agent ST101 demonstrated clinical activity and tissue treatment effect.
This data snapshot also demonstrated that patients receiving ST101 monotherapy exhibited encouraging response and survival outcomes.
Results from the ST101-101 study warrant further assessment of ST101 as part of a combination treatment approach for patients with rGBM.
Title: "Anti-tumor and Immunostimulatory Properties of ST316, a Peptide Antagonist of β-Catenin for Treatment of Cancers with Aberrant Wnt Pathway Activity"
Poster Number: B149
Session Title: Poster Session B
Date/Time: Friday, October 13, 2023, 12:30 pm-4:00 pm
Session location: Level 2, Exhibit Hall D

ST316, a first-in-class antagonist of β-catenin, is designed to selectively target oncogenic activation of the Wnt/β-catenin signaling pathway without impacting its activity in normal cells. ST316 is currently being evaluated in the Phase 1 portion of a Phase 1-2 study, ST316-101 (NCT05848739), which is a limited solid tumor basket study for tumors likely to harbor abnormalities in the Wnt pathway, such as colorectal cancers.
The poster summarized preclinical data demonstrating the anti-tumor and immunostimulatory properties of ST316 in multiple cancer models.
Key Conclusions:
ST316 effectively inhibits the transcriptional activity of oncogenic β-catenin, resulting in reduction of Wnt target genes involved in carcinogenesis, cell division, cell migration and immunoinhibitory processes.
ST316 treatment results in reduced cell viability and tumor growth inhibition, marked by the reduced expression of Wnt target genes within tumor tissue.
ST316 induces polarization of hPBMC-derived M2 macrophages toward the M1 phenotype and enhances CD8+ T cell activation in mixed cultures of macrophages and T cells. Furthermore, subpharmacologic ST316 augments the efficacy of anti-PD-1 antibody in an orthotopic 4T1 TNBC tumor model.
These findings underscore ST316’s potential as a therapeutic agent for targeting cancers characterized by aberrantly activated Wnt signaling pathways, showcasing its antitumor and immunostimulatory effects.
More information can be found on the AACR (Free AACR Whitepaper)-NCI-EORTC website.

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 advanced unresectable and metastatic solid tumors (NCT04478279). ST101-101 is an open-label, Phase 1-2 dose-finding study designed to determine the safety, tolerability, PK, PD, and proof-of-concept efficacy of ST101 in patients with advanced solid tumors. The study consists of two phases: Phase 1 dose escalation/regimen exploration and Phase 2 dose expansion. In the ongoing Phase 2 dose expansion part of the study, ST101 has demonstrated clinical proof-of-concept with a mRANO-confirmed partial response in a patient with recurrent GBM and evidence of long-lasting stable disease in several additional patients.

ST101 has been granted Fast Track designation for recurrent GBM and advanced cutaneous melanoma in patients who have disease progression on or after anti-PD-1/anti-PD-L1 therapy, as well as orphan designations from the FDA for Stage IIb-IV melanoma, glioma and AML, and from the European Commission for the treatment of glioma.

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 exposure in cancer cells prevents BCL9-driven nuclear localization of β-catenin and inhibits formation of the Wnt enhanceosome protein complex. Disruption of this interaction selectively suppresses the transcription of oncogenic Wnt target genes that regulate proliferation, migration, invasion and the metastatic potential of tumor cells, as well as genes that regulate the immunosuppression of the tumor microenvironment. ST316 creates a pro-immune tumor microenvironment and in preclinical models has shown to be synergistic with checkpoint inhibition. Due to its selectivity and downstream modulation of the Wnt/β-catenin pathway, ST316 presents an opportunity to safely and effectively target Wnt/β-catenin driven cancers without the toxicities previously seen with other Wnt pathway agents.

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 has begun enrolling and dosing patients with select advanced solid tumors that are known to harbor abnormalities of the Wnt/β-catenin signaling pathway. With its first patient dosed on June 5, 2023, the Company expects to complete the Phase 1 portion of the study in the second 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.