On October 13, 2023 ABION (KOSDAQ: 203400) reported data from an ongoing Phase 2 trial of ABN401, the company’s wholly owned tyrosine kinase inhibitor intended to treat adult patients with advanced non-small cell lung cancer that exhibit the MET Exon 14 skipping mutation (Press release, ABION, OCT 13, 2023, View Source [SID1234635963]). In eight treatment-naïve patients, the objective response rate was 75% (6/8), and in the evaluable population of 17 patients, the objective response rate was 52.9% (9/17).

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Patients were dosed 800 mg QD and the median duration of response was 5.4 months as of the data cut-off on July 25, 2023. The data are not mature enough to measure progression-free survival and duration of response. All patients are MET inhibitor naïve. Overall efficacy was comparable to currently marketed drugs and demonstrate superior efficacy in treatment-naïve patients.

The cut-off data reaffirm ABN401’s excellent safety profile as shown in an earlier Phase 1 trial. A total of 24 patients received ABN401 800 mg QD, including 17 METex14 NSCLC patients. Of 24 patients evaluable for safety, 2 (8.3%) experienced grades ≥3 treatment-related adverse events (TRAE). The most common treatment-related adverse events were nausea (70.8%), vomiting (29.2%), and diarrhea (33.3%). Grade ≥3 treatment-emergent adverse events occurred in 20.8% (5/24) patients. Treatment-related adverse events leading to permanent discontinuation occurred in none of the patients (0/24). Peripheral edema was observed in 29.2% (grade 1-2) and there was no grade 3 or greater event in all safety-evaluable populations, and 17.6% (grade 1-2) and 0% (grade 3) in METex14 NSCLC population. None of the patients discontinued treatment due to SAE or TRAE.

For the 17 METex14 NSCLC patients, one was not evaluable because the patient had not had the first tumor assessment at the time of the data cut-off. The median age is 69 (41-81) and 70.6% were male, with 1 (0-3) as the median prior lines of treatment. 41.2% of 17 patients were non-smokers and 58.8% were smokers. ABN401 continued to demonstrate outstanding safety compared to the currently marketed drugs.

The results were presented in a poster session 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) in Boston, and at a separate company event nearby.

"We are delighted to see the outstanding data from the global Phase 2 clinical trial to evaluate this potential best-in-class treatment, which continues to exhibit an outstanding safety profile," said Young Kee Shin, M.D., Ph.D., CEO of ABION. "Notably, these results follow and further expand the potential of ABN401 combination therapy with other treatment regiments. "The excellent safety enables the potential combination of ABN401 with EGFR treatment, chemotherapy, or KRAS or immuno-oncology treatments. Our goal is to increase options for patients with c-MET positive NSCLC."

Based on these results, ABION plans to initiate a Phase 2 combination trial with a multiple drug regimen. The c-MET mutation is the most common mutation shown by NSCLC patients after treatment with EGFR TKIs.

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.