On November 12, 2024 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported a Cooperative Research and Development Agreement (CRADA) has been executed to advance the development of camonsertib as an anticancer agent in collaboration with the Cancer Therapy Evaluation Program (CTEP) of the US National Cancer Institute (NCI), part of the US National Institutes of Health (Press release, Repare Therapeutics, NOV 12, 2024, View Source [SID1234648229]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"This partnership with the CTEP allows the research community to investigate the full clinical potential of camonsertib more easily and we believe it will provide additional clinical development catalysts for the program," said Lloyd M. Segal, President and Chief Executive Officer of Repare.

Camonsertib, a potential best-in-class oral small molecule ATR inhibitor, has demonstrated significant anti-tumor activity in preclinical and clinical studies. Ongoing clinical trials in patients with metastatic solid tumors are evaluating the safety and efficacy of camonsertib as monotherapy and in combination with Repare’s PKMYT1 inhibitor, lunresertib, with chemotherapy and with palliative external beam radiotherapy. Camonsertib monotherapy has demonstrated an encouraging signal of prolonged progression-free survival in patients with ATM-mutated non-small cell lung cancer. Recent Phase 1 results of camonsertib in combination with radiotherapy have shown benefit, including complete responses, in patients with ATM-altered tumors across various histologies.

The Cancer Therapy Evaluation Program (CTEP) of the NCI facilitates the development of promising cancer therapies by collaborating with researchers and industry partners. CTEP’s mission is to improve the lives of cancer patients by finding better ways to treat, control and cure cancer. CTEP is interested in combination studies involving camonsertib and various aspects of radiation therapy, and translational studies to identify predictive biomarkers.

On November 12, 2024 Cellworks Group Inc., a leader in Personalized Therapy Decision Support and Precision Drug Development, reported results from a study demonstrating the efficacy of the Cellworks Therapy Response Index (TRI) combined with personalized tumor microenvironment (TME) modeling in predicting overall survival (OS) for non-small cell lung cancer (NSCLC) patients receiving immunotherapy (IO) (Press release, Cellworks, NOV 12, 2024, View Source [SID1234648228]). This comprehensive approach enables more precise identification of patient-specific dysregulation in immunotherapy signaling pathways, resulting in better predictions of treatment responses.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Results from the study were showcased in a poster presentation titled, A Therapy Response Index Coupled with Personalized Tumor Microenvironment Modeling Predicts Overall Survival for Immunotherapy Treatment in NSCLC Patients, as part of the SITC (Free SITC Whitepaper) 2024 Annual Meeting held in Houston, Texas from November 6-10, 2024.

"In this study, we tackle one of the biggest challenges in cancer therapy today – accurately predicting how patients will respond to immunotherapy," said Dr. James Wingrove, Vice President of Clinical Solutions at Cellworks and presenting author for the study. "Although immunotherapy has demonstrated significant success in treating NSCLC, existing tools for predicting individual patient outcomes are inadequate. This research marks a crucial step forward in understanding the intricate relationship between tumor genomics and the tumor microenvironment, paving the way for more personalized and effective treatment strategies."

"This study highlights Cellworks’ commitment to advancing personalized oncology by providing tools that go beyond conventional prediction methods," said Dr. Michael Castro, Chief Medical Officer at Cellworks. "By integrating the Cellworks TRI score with detailed tumor microenvironment modeling, we’re able to offer a level of insight into immunotherapy outcomes that has the potential to transform how NSCLC patients are treated. This approach doesn’t just predict survival—it enables a deeper understanding of the unique cellular interactions within each patient’s tumor, opening the door to more effective, personalized treatment strategies."

Study Design

The study involved the development and validation of an algorithm to deconvolute cell proportion and cell-specific gene expression from bulk transcriptome data. Utilizing a reference matrix generated from single-cell NSCLC data (n=771,891 cells), the algorithm was applied to RNA-seq data from 63 NSCLC patients who had received immunotherapy. A personalized Computational Biosimulation Model (CBM) of tumor genomic networks was generated for each patient using whole exome sequencing data, and a Therapy Response Index (TRI) score was calculated.

Study Results

The tumor microenvironment composition significantly predicted overall survival in NSCLC patients, as shown in a Cox proportional hazards model (LR ꭓ² = 20.12, p-value = 7.29e-6, HR = 0.157). Combining the TRI score with tumor microenvironment cell proportions (TCP) further improved the model’s ability to predict OS (LR ꭓ² = 24.21, p-value = 8.63e-07, HR = 0.11). The study revealed specific immune markers correlated with improved outcomes, including the ratio of CXCL9+ M1-like macrophages to SPP1+ CD163+ M2-like macrophages, which positively correlated with longer survival. Patients with high interferon+ macrophages and higher activated CD8+ T cells also demonstrated better outcomes, while elevated neutrophil presence was associated with reduced survival.

The Cellworks Platform, CBM and TRI

The Cellworks Platform performs computational biosimulation of protein-protein interactions, enabling in silico modeling of tumor behavior using comprehensive genomic data. This allows for the evaluation of how personalized treatment strategies interact with the patient’s unique tumor network. Multi-omic data from an individual patient or cohort is used as input to the in silico Cellworks Computational Biology Model (CBM) to generate a personalized or cohort-specific disease model. The CBM is a highly curated mechanistic network of 6,000+ human genes, 30,000 molecular species and 600,000 molecular interactions. This model along with associated drug models are used to biosimulate the impact of specific compounds or combinations of drugs on the patient or cohort and produce therapy response predictions, which are statistically modeled to produce a qualitative Therapy Response Index (TRI) score, scaled from 0 (unfavorable outcome) to 100 (favorable outcome) for a specific therapy. The Cellworks CBM has been tested and applied against various clinical datasets with results provided in over 125 presentations and publications with global collaborators.

On November 12, 2024 GlycoNex, Inc. (4168, hereinafter referred to as GNX), a clinical stage biotechnology company focused on the development of glycan-directed cancer immunotherapies, reported a manufacturing agreement with Sterling Pharma Solutions, a UK-based CDMO with a specialist Antibody-Drug Conjugate (ADC) division, for clinical trial production of GNX102-ADC in preparation for a planned Phase 1 clinical program investigating the drug technology (Press release, GlycoNex, NOV 12, 2024, View Source [SID1234648227]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

GNX102-ADC combines GlycoNex’s proprietary monoclonal antibody (mAb), GNX102, and cytotoxic drug therapies to elicit cellular cytotoxicity to target cancer cells with high specificity. GNX102 is a humanized mAb designed to target novel tumor-associated glycans to inhibit tumor growth. GNX102 successfully completed Phase 1 clinical trials with data demonstrating strong safety and tolerability.

"Our GNX102 monoclonal antibody demonstrated superior safety in Phase 1 clinical trials making it an ideal candidate to develop as an ADC," said Dr. Mei-Chun Yang, CEO of GlycoNex. "We are excited to benefit from Sterling’s ADC manufacturing expertise in the production of GNX102-ADC as we seek to investigate the technology’s ability to bind antibodies to cancer cell antigens, initiating apoptotic cell death while directly delivering cytotoxic drugs to the tumor."

Commenting on the partnership, Chad Telgenhof, Chief Commercial Officer at Sterling Pharma Solutions added, "As a company, Sterling continues to invest in capabilities to support ADC innovator companies, in what is a strong and growing area of research. This agreement will leverage the expertise we have in clinical-scale GMP manufacturing at our site in Deeside, UK, and we look forward to building a partnership with GlycoNex to support its ongoing drug development."

Data from the preclinical trials of GNX102-ADC demonstrated safety comparable to approved ADCs with the potential to treat a range of solid tumors, including gastric cancer, colorectal, pancreatic, and lung cancers. In addition, GNX102-ADC has shown strong tumor-suppressing potential in preclinical animal studies. GlycoNex retains full development rights for GNX102-ADC, with patents secured in key global markets, including the U.S., Japan, South Korea, Taiwan, and Russia.

The global ADC market size was valued at USD 11.65 billion in 2023 and is anticipated to reach approximately USD 28.61 billion by 2033, growing at a CAGR of 9.4% from 2024 to 2033.i GlycoNex is well positioned to capitalize on this opportunity with its comprehensive in-house capabilities for end-to-end antibody drug development. GlycoNex’s advanced capabilities supports the full drug development cycle, from monoclonal antibody discovery and preclinical studies to manufacturing and clinical development, ensuring a seamless and efficient transition from laboratory research to clinical trials.

On November 12, 2024 Bexion Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company developing a novel class of biologic therapy to treat solid tumor cancers and chemotherapy-induced peripheral neuropathy (CIPN), reported that the Company will participate in the Jefferies London Healthcare Conference (Press release, Bexion, NOV 12, 2024, View Source [SID1234648226]). The conference will be held in London, UK, from November 19-21, 2024.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Jim Beach, CEO and President of Bexion Pharmaceuticals, and Joyce LaViscount, Chief Financial Officer of Bexion Pharmaceuticals, will attend the conference.

About BXQ-350
Bexion’s lead drug candidate is BXQ-350, a first-in-class biologic containing the multifunctional, sphingolipid activator protein, Saposin C, and a phospholipid. Multiple Phase 1 clinical trials in adult and pediatric patients have demonstrated a robust safety profile for BXQ-350 with evidence of single agent activity across multiple solid tumor types. Additionally, other clinical and non-clinical data suggest BXQ-350 has activity in chemotherapy-induced peripheral neuropathy, an area of high unmet medical need in patients treated with oxaliplatin and other chemotoxic agents.

On November 12, 2024 Flare Therapeutics Inc., a clinical-stage biotechnology company targeting transcription factors to discover precision medicines for oncology and other therapeutic areas, reported it has entered into a strategic discovery collaboration with Roche (SIX: RO, ROG; OTCQX: RHHBY) (Press release, Flare Therapeutics, NOV 12, 2024, View Source [SID1234648225]). This partnership will leverage Flare Therapeutics’ proteomic and mass spectrometry platform and expertise, powered by its proprietary library of electrophilic compounds, to discover novel small molecule drugs aimed at previously undrugged transcription factor targets in oncology.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Roche is an ideal partner for Flare Therapeutics because we share a commitment to tackling the most challenging disease areas with novel approaches and overcoming the difficulties of drugging transcription factors. Our platform and expertise have rapidly generated a clinical-stage pipeline, demonstrating the strong potential of our approach. This collaboration will accelerate the expansion of our capabilities, enabling us to develop treatments for transcription factors implicated in indications with high unmet needs. Together with Roche’s expertise, our objective is to successfully pursue challenging transcription factor targets, with the ultimate goal of providing novel interventions for patients who are not currently served by standard-of-care therapies," said Rob Sims, Ph.D., Chief Scientific Officer and Co-founder of Flare Therapeutics.

"We are excited to join forces with Flare Therapeutics, combining our leading expertise and global reach in oncology with Flare Therapeutics’ deep knowledge in drug discovery for difficult-to-drug transcription factor targets. Transcription factors play a crucial role in various oncological diseases and have the potential to address high unmet medical needs. We are looking forward to developing therapeutic options never possible before," said Boris L. Zaïtra, Head of Roche Corporate Business Development.

As part of the collaboration, Flare Therapeutics will receive a US$70 million upfront cash payment and is eligible to receive discovery, development, and commercialization milestone payments potentially exceeding US$1.8 billion and royalties. Flare Therapeutics will lead discovery and preclinical activities targeting multiple transcription factor targets in oncology, while Roche will pursue the further preclinical and clinical development and commercialization of potential products from the collaboration, leveraging its industry-leading capabilities in oncology.

Additionally, Flare Therapeutics retains a right to co-fund development for one target under the collaboration in exchange for increased royalties in the United States for this target. Flare Therapeutics will retain ownership of its existing pipeline, including its lead clinical-stage program, FX-909, in advanced urothelial cancer, its prostate cancer program entering IND-enabling studies, and other programs in discovery and early development in oncology and other therapeutic areas.